Results showed hyperphosphorylated tau mainly occurred in hypoglossal, dorsal motor vagal, trigeminal sensory/motor nuclei as well as in dorsal raphe, locus coeruleus and substantia nigra. 
While acute administration of the tachykinin NK1 receptor antagonist CP-96,345 (10 mg/kg, i.p.) attenuated the responsiveness of dorsal raphe 5-HT(1A) autoreceptors, lesioning noradrenaline neurons with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) prevented the enhancing action of a 2-day treatment with CP-96,345 on 5-HT neuronal firing, suggesting that tachykinin NK1 receptor antagonists influence 5-HT system via noradrenaline neurons independently of their firing rate..
Recent studies have reported that the vesicular glutamate transporter VGLUT3 is found in both serotonergic and nonserotonergic neurons in both the median raphe (MR) and dorsal raphe (DR) nuclei.
For all drugs tested, reductions of NET and SERT protein were not accompanied by reduced NET or SERT mRNA in locus coeruleus or dorsal raphe nucleus, respectively.
These effects are possibly mediated by interactions of neurotensin with neurons releasing DA or 5-HT, projecting to the PFC from the ventrotegmental area (VTA) and from the dorsal raphe nuclei (DRN), respectively.
However, the net stimulation of [ (35)S]GTPgammaS binding induced by the 5-HT(1A) agonist 8-OH-DPAT was significantly attenuated in dorsal raphe nucleus (DRN), but not in hippocampus, after chronic fluoxetine. The inhibition of dorsal raphe firing by 8-OH-DPAT was also attenuated in fluoxetine-treated rats (ED(50) = 2.12 +/- 0.32 mug/kg and 4.34 +/- 0.09 mug/kg, for vehicle and fluoxetine respectively), an effect which was also prevented by the concomitant administration of WAY100635 (ED(50) = 2.10 +/- 0.58 mug/kg).
The in vivo relevance of the antagonistic effect of R-citalopram on escitalopram efficacy was confirmed in dorsal raphe nucleus, a brain region known to be a target for SSRIs.
Here we report that stimulation of the dorsal raphe nucleus (DRN) in freely moving rats produces profound effects on the electroretinogram (ERG). Most notably, activation of the dorsal raphe-retinal pathway causes a significant decrease in the latency of the b-wave and accompanying oscillatory potentials. In addition, dorsal raphe stimulation leads to a significant increase in the amplitude of oscillatory potentials.
Anxiety-related behavior was tested in an open field, and design-based stereology was used for counting serotonergic (5-hydroxytryptamine/serotonin, 5-HT) neurons in the dorsal raphe nucleus (DRN).
As bursting has been found to be physiologically relevant for the synaptic release of serotonin (5-HT), we investigated the possible role of SK channels in the control of this firing pattern in 5-HT neurons of the dorsal raphe nucleus.
The expression of mRNA for 5HTT in the dorsal raphe was determined on in situ hybridization.
Serotonergic neurons of the dorsal raphe nucleus (DRN) fire at a steady rate during W, decrease their firing during SWS and virtually cease activity during REMS.
The neurodegenerative processes underlying PD result in loss of serotonin (5-HT) input from the dorsal raphe nucleus (DRN) to the striatum, but to a lesser extent than loss of dopamine input.
The dorsal raphe nucleus (DRN) is a heterogeneous brainstem nucleus located in the midbrain and pons.
Finally, since stereotaxic accuracy is crucial for quantification in most microprobe studies, the influence of stereotaxic positioning error was studied for several realistic experiments in favorable and unfavorable experimental situations (binding of (11)C-Raclopride to D2 dopaminergic receptors in the striatum; binding of (18)F-MPPF to 5HT1A receptors in the dorsal raphe nucleus)..
Interestingly, using in situ hybridization experiments indicated that TrkB receptor mRNA was expressed in the hippocampus and dorsal raphe nucleus in adult mice suggesting that the neurochemical and behavioral effects of intra-hippocampal BDNF injection can mobilize both pre- and post-synaptic elements of the brain 5-HT neurotransmission.
The axons of certain dorsal raphe neurons form a dense serotonergic supraependymal plexus lining the brain ventricles, likely regulating ependymal metabolism and activity including ciliary movements and glucose homeostasis.
On the other hand, atypical antipsychotic drugs might further act upon 5-HT2A, 5-HT1A and alpha1-adrenoceptors present in pyramidal cells (including those projecting to the dorsal raphe nucleus), which would directly inhibit an excessive excitability of these cells..
Based on post-mortem studies analyzing mRNA expression by in situ hybridization, serotonergic neurons from the dorsal raphe nucleus (DRN) from depressive suicide victims are seen to over-express cytochrome oxidase mRNA.
Analysis of imaging data demonstrates an increase in MRI signal for all the regions of interest selected including the rostral ventromedial medulla, dorsal raphe, periaqueductal grey, medial thalamus, and central amygdala as predicted by the anatomical data, as well as increases in the lateral thalamus, cingulate/retrosplenial and parietal cortex.
The hypocretinergic (HCRT) neurons of the perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) are mostly active during waking and have been implicated in the regulation of arousal.
Using three-photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe.
The present study was conducted to examine the effects of prolonged bupropion administration on the firing activity of dorsal raphe nucleus (DRN), locus coeruleus (LC), and ventral tegmental area (VTA) neurons.
Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. Infusions of CRF (0.5 microg/0.5 microL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 microL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25-50 ng/0.5 microL) or antisauvagine-30 (2 microg/0.5 microL), respectively. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe.
Double-labeling experiments show that GIRK subunits are present in most of the 5-HT(1A) receptor-expressing cells in hippocampus, cerebral cortex, septum, and dorsal raphe nucleus. Similarly, GIRK mRNA subunits are found in glutamatergic and GABAergic neurons in hippocampus, cerebral cortex, and thalamus, in cholinergic cells in the nucleus of vertical limb of the diagonal band, and in serotonergic cells in the dorsal raphe nucleus.
In this study we tested the hypothesis that 5-HT activity in the dorsal raphe nucleus (DRN) contributes to the acquisition and expression of conditioned defeat.
Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus.
The reduced synthesis was also observed in the dorsal raphe (DR) nucleus and the median raphe (MR) nucleus.
The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception.
They depolarize many types of central neurons and can increase [ Ca(2+)](i) in some, including those of the dorsal raphe (DR) and laterodorsal tegmental (LDT) nuclei-two structures likely to contribute to the behavioral actions of Hcrt/Orx.
Social interaction-induced neuronal activation patterns were studied in the prefrontal cortex (orbitofrontal and medial), amygdala (central, medial, and basolateral), dorsal raphe and locus coeruleus.
We present an overview of our studies on the differential role of serotonergic projections from the median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) in behavioural animal models with relevance to schizophrenia.
In turn, both parasympathetic and adrenergic medullary circuitries are regulated by the pontine A5 noradrenergic (NA) and the dorsal raphe serotonergic nuclei, respectively.
Acute MDMA in-vitro application on slices of the dorsal raphe nucleus (DRN) induced concentration-dependent 5-HT release and 5-HT cell firing inhibition.
The rat trigeminal somatosensory system has been studied extensively and receives serotonergic afferents from the dorsal raphe nucleus.
ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe.
The current study examined whether chronic amphetamine treatment (2.5mg/kg, 14 days) or withdrawal altered CRF receptor densities in the serotonergic dorsal raphe nucleus (dRN).
For this purpose, the effects of a lesion of the dorsal raphe nucleus (DRN) by 5,7-dihydroxytryptamine (5,7-DHT) on the action of tramadol (20 mg/kg, i.p.) on depression-related behavior and neurochemical correlates were investigated in mice.
We describe the effects of perfusion of living rat brain slices with tryptophan on both 1) tissue concentrations of serotonin metabolites and 2) neuronal firing rates within the dorsal raphe nucleus. Tryptophan resulted in time-dependent and concentration-dependent increases in serotonin and serotonin metabolites, effects that were correlated with restoration of tonic autoinhibition of dorsal raphe nucleus neuronal firing rates.
However, neuropathological differences were absent in the dorsal raphe nuclei, amygdala, and cortical regions.
Serotonin (5-HT) containing neurons in the dorsal raphe nucleus (DRN) may play important roles in Parkinson's disease (PD).
We have previously shown that chronic antidepressant treatments increase the binding of a GalR2-preferring ligand, galanin (2-11), to the dorsal raphe nucleus (DRN) of the rat, which, along with the finding that intra-DRN infusion of galanin (2-11) increases the release of serotonin in the hippocampus, suggests that GalR2 signaling might exert antidepressant-like actions by modulating ascending serotonergic outflow.
The present study was performed to test two hypotheses: (1) that potentials in the domain of seconds (0.1-0.5 Hz) reflect specific and direct interactions of the MGN and A1 during neural processing of sensory information, and (2) that low-frequency infraslow potentials in the A1 (<0.1 Hz) are related to brainstem influences originating from the locus coeruleus (LC) and dorsal raphe nucleus (DRN).
Using in-vivo electrophysiological and behavioural paradigms in the rat, the effects of bifeprunox and aripiprazole were assessed on ventral tegmental area (VTA) dopamine and dorsal raphe serotonin (5-HT) cell activity and on foot shock-induced ultrasonic vocalisation (USV).
However, only limited investigations have examined the effects of MDMA on the dorsal raphe nucleus. The present study was designed to assess the effect of MDMA on the rate-limiting enzyme in 5-HT biosynthesis, tryptophan hydroxylase (TPH), by measuring TPH2 protein and mRNA levels in rat dorsal raphe (DR) nucleus.
failure to learn, exaggerated fear, dorsal raphe nucleus (DRN) 5-HT activation).
This was done by testing the effect of systemic blockade of 5-HT-1A receptors on Fos expression in 5-HT neurons in the dorsal raphe (DR) and median raphe (MR).
In this study, we asked if functional nAChRs are present in serotonergic (5-HT) and nonserotonergic (non-5-HT) neurons of the dorsal raphe nucleus (DRN).
Recent studies using anterograde and retrograde tracers have shown that vestibular nuclei are targeted by regionally selective projections from the serotonergic dorsal raphe nucleus.
Using a nonhuman primate model of surgical menopause, our laboratory has shown that ovarian hormone treatment (HT) improves 5-HT neural function in the dorsal raphe nucleus (DRN). AIF was immunocytochemically localized to large 5-HT-like neurons of the dorsal raphe.
To elucidate the functional relationship between serotonin neurons and dopamine neurons, we performed single-unit recording in the dorsal raphe nucleus (DRN), a major source of serotonin, and the substantia nigra pars compacta, a major source of dopamine, while monkeys performed saccade tasks in which the position of the target indicated the size of an upcoming reward.
The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle.
The primary goal of this study was to identify the collateral projection from the dorsal raphe (DR) nucleus to whisker-related, trigeminal sensory and facial motor systems in the rat.
A main characteristic of emotion-related brain regions (orbitofrontal cortex, anterior cingulated cortex, amygdala, insula) is their reciprocal anatomical connectivity with each other as well as with neuromodulatory systems (e.g., serotonergic dorsal raphe, cholinergic nucleus basalis of Meynert, and dopaminergic ventral tegmentum) and with other brain areas involved in sensory, motor, and cognitive functions.
A growing body of evidence from preclinical rodents models, and especially genetically modified mice and inbred mouse strains, has provided significant insight into how genetic variation in these molecules can affect the development and function of a key neural circuit between the dorsal raphe nucleus, medial prefrontal cortex and amygdala.
The dorsal raphe nucleus (DRN) contains both serotonergic and nonserotonergic projection neurons.
The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of limbic structures crucial for the regulation of emotionally influenced behaviour.
Neuropathological examination demonstrated abundant Lewy-related pathology including Lewy bodies and neurites in the hippocampal region and the cerebral cortex, and moderate levels in brain stem nuclei including the substantia nigra, locus ceruleus and dorsal raphe nucleus.
Therefore in this study it was examined how alpha4-containing receptors are positioned to modulate the function of 5-HT neurons using ultrastructural analysis of immunolabeling for the alpha4 receptor subunit in the dorsal raphe nucleus (DR), a primary source of forebrain 5-HT in the rat.
These include: the medial preoptic nucleus; median and lateral preoptic area; medial division of the bed nucleus of stria terminalis; paraventricular nucleus; central nucleus of the amygdala; dorsal hypothalamic area/dorsomedial hypothalamus; lateral hypothalamic area; lateral, ventrolateral and dorsomedial divisions of the periaqueductal grey; dorsal raphe nuclei; parabrachial nuclei; Kölliker-Fuse nucleus; intertrigeminal region; rostral ventrolateral medulla; lateral parafacial region; and the ventral respiratory group.
In addition, SNC80 also significantly reversed the loss of TH-positive cells produced by OBX in the dorsal raphe.
Eight regions of interest were defined a priori (orbitofrontal cortex, amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus and cerebellum as reference).
Within the dorsal raphe nucleus, neither 5-HT(1A) nor 5-HTT mRNA expression differed between those who committed suicide and control subjects.
We measured TRP, KYN and 5-HT contents in the prefrontal cortex, hippocampus, amygdala and dorsal raphe nuclei to investigate the balance between the KYN and 5-HT pathways.
Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats.
By using anterograde tract-tracing, we further showed that the DPGi, in addition to locus coeruleus, directly projected to other areas containing wake-promoting neurons such as the serotonergic neurons of the dorsal raphe nucleus and hypocretinergic neurons of the posterior hypothalamus.
The intra-dorsal raphe infusion of 0.03 microg epibatidine induced significant excitation of locus coeruleus neurons.
Microinjection of m-CPBG (2.0 and 4.0 mM) into the dorsal raphe nucleus (DRN) decreased rapid-eye-movement sleep (REMS) and the number of REM periods during the first, second, and third 2-h recording period.
5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females.
The effect of chronic citalopram or escitalopram administration on 5-HT1A receptor function in the dorsal raphe nucleus was determined by measuring [ 35S]GTP gamma S binding stimulated by the 5-HT1A receptor agonist (R)-(+)-8-OH-DPAT (1nM-10 microM). As the binding and action of escitalopram is limited by the inactive enantiomer R-citalopram present in racemic citalopram, we propose that the regulation of 5-HT1A receptor function in the dorsal raphe nucleus at the level of receptor-G protein interaction may be a result of greater inhibition of the serotonin transporter by escitalopram..
In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons.
These data are congruent with the hypothesis that carbachol-inhibited GABAergic PnO neurons project to, and inhibit, REM-on SubC reticular neurons during waking, whereas carbachol-excited SubC and PnO GABAergic neurons are involved in silencing locus coeruleus and dorsal raphe aminergic neurons during REM sleep.
Furthermore, to study the significance of some distinctive central nuclei in these processes, and the metabolism of 5-HT in the hypothalamus and the dorsal raphe nucleus (DRN). Stereotactically neurotoxic lesion with 5,7-dihydroxy-5-HT in the dorsal raphe nucleus (DRN) or the hypothalamic paraventricular nucleus (PVN) reduced the ACTH and AVP response to stress, indicating an importance of these structures for this response.
The selective lesion of DA neurons elicited by 6-hydroxydopamine (6-OHDA) decreased the spontaneous firing activity of dorsal raphe (DR) nucleus 5-HT neurons by 60%, thus revealing the excitatory effect of the DA input on these 5-HT neurons.
The expression of galanin and galanin receptor-2 in hippocampus and dorsal raphe nucleus of depression model was studied. The method of in situ hybridization was used for testing the expression of Galanin and galanin receptor-2 in hippocampus and dorsal raphe nucleus and the method of RT-PCR was used to further analysis of the expression. The expression of Galanin and its receptor-2 in hippocampus and dorsal raphe nucleus increased obviously.
We show here that in the rat dorsal raphe nucleus (DRN), the nucleus that contains the highest number of 5-HT neurons in the brain, TPH1 mRNA reveals a low level of expression but is detectable both by quantitative real-time PCR and in situ hybridization whereas in the pineal gland (PiG), TPH1 mRNA is strongly expressed.
This positron-emission tomography (PET) study tested the hypothesis that 5-HT(1A) autoreceptor internalization might be indexed in vivo by a decrease in the specific binding of the 5-HT(1A) radioligand, 4-[ 18F]fluoro-N-[ 2-[ 1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide ([ (18)F]MPPF), in the dorsal raphe nucleus (DRN) of healthy adult men administered a single oral dose of the selective serotonin reuptake inhibitor, fluoxetine.
Using a phospho-selective antibody directed against the activated KOR to image sites of dynorphin action in the brain, we found that stress and CRF each caused dynorphin-dependent KOR activation in the basolateral amygdala, nucleus accumbens, dorsal raphe, and hippocampus.
We sought the effect of estradiol (E) and progesterone (P) on survival gene expression in laser captured serotonin neurons and in the dorsal raphe region of monkeys with cDNA array analysis. First, RNA from a small block of midbrain containing the dorsal raphe was hybridized to Rhesus Gene Chips (n = 3/treatment).
Serotonin-1A (5-HT(1A) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission.
Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides.
The present study on rat examined the role of galanin receptor subtypes in regulation of depression-like behavior as well as potential molecular mechanisms involved in the locus coeruleus (LC) and dorsal raphe (DR).
A single injection of dexamethasone did not affect mRNA expressions of TPH, MAO-A and 5-HTT genes, but repeated dexamethasone increased them in the dorsal raphe nucleus.
AIM: The 5-HT(1A) receptor antagonist 4-Iodo-N-[ 2-[ 4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (10 microM) was perfused into the dorsal raphe nucleus (DRN) to study simultaneously the effects of the drug on the DRN and frontal cortex extracellular serotonin (5-hydroxytryptamine, 5-HT) levels and concurring behavioural states.
CTb-positive fibers were seen in the lateral region of the dorsal raphe nucleus (DR) on the side contralateral to the injection, and a few labeled perikarya were observed in the lateral portion of the DR on the ipsilateral side.
In the present study, the pharmacologic properties of Wf-516 were thus assessed using in vivo electrophysiology in the rat dorsal raphe nucleus (DRN), locus coeruleus (LC) and hippocampus.
RESULTS: The authors found no significant difference in the binding potential of [ 11C]DASB between the recovered depressed patients and healthy comparison subjects in any of the brain regions (amygdala, anterior cingulate cortex, caudate nucleus, frontal cortex, hippocampus, insula, thalamus, and dorsal raphe) studied.
The dorsal raphe nucleus (DRN)-serotonin (5-HT) system plays a key role in stress-related psychiatric disorders such as anxiety and depression.
Finally, a CSP pressure response identical to micturition was evoked in and around the Barrington's nucleus and in the dorsal raphe nucleus.
No significant (+)8-OH-DPAT-induced changes in pERK were observed in dorsal raphe or amygdala.
The neuropeptide galanin and its three receptor subtypes (Gal R1-3) are highly expressed in the dorsal raphe nucleus (DRN), a region of the brain that contains a large population of serotonergic neurons.
Nonsignificant increases, ranging between 9% and 19%, were recorded in the whole auditory system, CA1 pyramidal cell layer, and dorsal raphe.
Of the labelled cell bodies in the subcortical structures, about 38.8% were located in the ipsilateral basal forebrain (10.6% in the lateral amygdala LA, 11.5% in the globus pallidus GP, 3.7% in the ventral pallidum VPa, 13.0% in the nucleus basalis NB), 13.1% in the ipsi- and contralateral diencephalon (6.4% in the posterior paraventricular thalamic nuclei, 6.7% in the hypothalamic area), and 48.1% in the midbrain (20.0% in the ipsilateral substantia nigra, 9.8% in the ipsi- and contralateral ventral tegmental area, 5.0% in the ipsi- and contralateral locus coeruleus, 13.3% the ipsi- and contralateral dorsal raphe nuclei).
Electrical stimulation of the pinna induced significant increases in the number of Fos-positive neurons in the DCN, spinal trigeminal nucleus (Sp5), dorsal raphe nucleus (DR) and locus coeruleus (LC).
Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism.
Acute VNS significantly increased c-Fos staining in the nucleus of the solitary tract, paraventricular nucleus of the hypothalamus, parabrachial nucleus, ventral bed nucleus of the stria terminalis, and locus coeruleus but not in the cingulate cortex or dorsal raphe nucleus (DRN).
Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative RT-PCR techniques, we have examined the effects of fluoxetine administration with drinking water (7.5 mg/kg/day) for 2, 4 and 8 weeks on TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus (DRN) and in the brainstem containing the rest of the raphe complex.
Interestingly, we found increased DA levels in the striatum following acute MAP exposure; these increased levels were reversed by pretreatment with MDL 72222, but did not affect 5-HT levels in the dorsal raphe.
The interaction force assessments from the robot reveal significant differences between spinalized control rats, and rats receiving implants of E14 dorsal raphe tissue to provide a serotonin source.
We found that bilateral HFS of the STN consistently inhibited (40-50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons.
We have developed dissociated primary cultures of the dorsal raphe nucleus from postnatal 9-12-day-old rats.
The effects of microinjection of the nitric oxide (NO) precursor l-arginine (l-Arg), the NO synthase (NOS) inhibitors N-methyl-l-arginine (l-NAME) and 7-nitroindazole (7-NI), and the cyclic guanosine 3',5'-monophosphate (cGMP) analog 8-Br-cGMP into the dorsal raphe nucleus (DRN) were assessed in rats using the elevated plus maze (EPM) and the forced swim test (FST).
This inhibitory effect was significantly (P<0.05) attenuated after pretreatment with para-chlorophenylalanine (pCPA), or electrolytic lesion of dorsal raphe (DR) nucleus.
This therapeutic activity could be mediated via stimulation of serotonin (5-HT) neurons located in the dorsal raphe nucleus (DRN), which receive important SP-NK1 receptor immunoreactive innervations.
Rats were implanted with a monopolar stimulation electrode aimed at the lateral hypothalamus, ventral tegmental area, dorsal raphe or median raphe nuclei, and a lesioning electrode in the ipsilateral habenula. Histological analysis revealed that in two rats the stimulation electrode was located in the posterior lateral hypothalamus, two in the anterior ventral tegmental area and one in the area of the dorsal raphe.
Tissue content of 5-HT, 5-HIAA and 5-HT turnover (ratio 5-HIAA/5-HT) were determined in a sample containing i) the median and dorsal raphe nuclei, ii) the frontal cortex, or iii) the ventral hippocampus ex vivo.
In the dorsal raphe nucleus, a 2-week treatment with escitalopram (10 mg/kg/day, subcutaneous) did not modify the firing activity of 5-HT neurons, whereas a cotreatment with R-citalopram (20 mg/kg/day, subcutaneous) decreased it.
In addition, GBP-induced increase in c-Fos expression was observed in the dorsal raphe (DRN) and in the nucleus raphe magnus.
Since the NI is located just caudal to the dorsal raphe nucleus where abundant serotonin (5-HT) neurons are present, we examined if 5-HT effects on the expression of relaxin 3.
In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN).
In the present study, the effects of Acanthopanax senticosus on the time to exhaustion by treadmill exercise and on 5-HT synthesis and TPH expression in the dorsal raphe were investigated by immunohistochemistry. Acanthopanax senticosus was effective as caffeine for increasing the exhaustion time in treadmill running and for reducing the exercise-induced increase of 5-HT synthesis and TPH expression in the dorsal raphe. The present study shows that Acanthopanax senticosus reduces fatigue during exercise by the inhibition of exercise-induced 5-HT synthesis and TPH expression in the dorsal raphe..
The present study was undertaken to elucidate whether early postnatal stress affects rat brain development and influences the serotonergic function in the midbrain median raphe nuclei (MRN) and dorsal raphe nuclei (DRN) in the adult, focusing on the response to unconditioned fear stress.
Electrophysiological, microdialysis and behavioral studies support a modulatory role for corticotropin-releasing factor (CRF) in regulating the dorsal raphe nucleus (DRN)-serotonin (5-HT) system.
CPP intensity was inversely correlated with 5-HT(1A) BP in multiple cortical and subcortical areas, including the prefrontal and cingulate cortices, insula, amygdala and the dorsal raphe.
More than half of the CTb-Fos double-labelled neurons were located in the prefrontal cortex, lateral preoptic area-lateral hypothalamus, pontomesencephalic tegmentum, dorsal raphe nucleus, ventral pallidum and nucleus accumbens.
EXPERIMENTAL APPROACH: Single cell extracellular recordings of dorsal raphe (DR) neurones were performed in rat brain slices.
RESULTS: After correction for multiple comparisons, the four groups showed significant (p<0.05) differences for [ 11C]McN5652 BP values for the dorsal raphe and antero-ventral striatum (AVS).
We also showed that the tonic inhibition of locus coeruleus (LC) noradrenergic and dorsal raphe (DRN) serotonergic neurons during sleep is due to a tonic GABAergic inhibition by neurons localized in the dorsal paragigantocellular reticular nucleus (DPGi) and the ventrolateral periaqueductal gray (vlPAG).
Single neuron firing rate was recorded from dorsal raphe nucleus of anesthetized rats. The glycine transporter type-1 (GlyT1) antagonists Org-24461 (10 mg/kg i.v.) and NFPS (3 mg/kg i.v.) reversed the inhibitory effect of L-701,324 on single neuron activity recorded from dorsal raphe nucleus of the rat.
Additionally, Cre-mediated DNA recombination was restricted to neuronal populations that express the receptor, e.g., cerebral cortex, septum, hippocampus, dorsal raphe, thalamic, hypothalamic and amygdaloid nuclei, and spinal cord.
The purpose of the research was to reveal the features of neurotensin (administered in substantia nigra or dorsal raphe nucleus) effect on recall of passive avoidance reactions in rats. On the contrary, injection of the substance in the dorsal raphe nucleus led to an intensification of these reactions and delay of their extinction.
Serial sections were immunostained for tryptophan hydroxylase (TrOH) and alpha-synuclein and cell counts were performed in the dorsal raphe (DR), median raphe (MR) and medullary raphe nuclei.
In electrophysiological studies SB-649915 had no effect on rat dorsal raphe neuronal cell firing per se, but reversed 8-OH-DPAT-induced inhibition of firing both in vitro and in vivo.
In particular, the paper discusses the impact of sciatic nerve ligature on genomic and biochemical components of neurosteroidogenesis in the spinal cord and brainstem areas including the parabrachial, raphe magnus and dorsal raphe nuclei which control nociception.
Importantly, the ILS mice also had a significantly greater number of Ucn1-positive terminal fibers than ISS mice in the lateral septum and the dorsal raphe nucleus, projection areas of Ucn1-containing neurons. These results suggest that the greater sensitivity of ILS than ISS mice to the hypothermic effects of ethanol could be mediated by stronger innervation of the dorsal raphe by Ucn1-containing fibers. In addition, these results lend further support to previous findings implicating Ucn1-containing projections from npEW to the dorsal raphe in ethanol-induced hypothermia..
Swim stress regulates forebrain 5-hydroxytryptamine (5-HT) release in a complex manner and its effects are initiated in the serotonergic dorsal raphe nucleus (DRN).
The authors hypothesized that repeated rewarding electrical stimulation of the dorsal raphe can produce behavioral sensitization to psychostimulants.
To better understand the delay of neurological maturation in MS2-15 rats, we determined the levels of various monoamines in different regions of the brain stem, including the vestibular area, the substantia nigra, ventral tegmental area and dorsal raphe nuclei.
Dopamine produced from L-DOPA is degraded by endogenous monoamine oxidase in neurons of the dorsal raphe nucleus of the rat: an immunohistochemical study.
In the rat, galanin-like immunoreactivity is expressed in a population of 5-hydroxytryptamine (5-HT, serotonin) neurons in the dorsal raphe with extensive projections to the forebrain areas, e.g., hippocampus. Galanin, given intracerebroventricular (i.c.v.), was demonstrated to have strong inhibitory interactions with 5-HT1A receptor functions, particularly in the dorsal raphe but also in the hippocampus. Since pre- and postsynaptic 5-HT1A receptors in the dorsal raphe and hippocampus are implicated in the action of antidepressant drugs and in depressive disorders, it is suggested that galanin receptors may be an important target for development of novel antidepressant drugs.
Corticotropin-releasing factor (CRF) has been shown to affect serotonergic neurons in the dorsal raphe nucleus (DRN) and to modulate learned helplessness via a CRF type-2 receptor (CRF-R2) mechanism.
Placebo treatment affected endogenous opioid activity in a number of predicted mu-opioid receptor-rich regions that play central roles in pain and affect, including periaqueductal gray and nearby dorsal raphe and nucleus cuneiformis, amygdala, orbitofrontal cortex, insula, rostral anterior cingulate, and lateral prefrontal cortex.
Brainstem 5-HT1A somatodendritic autoreceptors regulate serotonin neuron firing but studies of autoreceptor binding in the dorsal raphe nucleus (DRN) in depressed suicides report conflicting results.
To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs.
Serotonin (5-HT) and the dorsal raphe nuclei (DRN) have been implicated in the inhibitory control of salt intake (i.e., sodium appetite).
Up to P15.5 no differences were apparent in the differentiation and distribution of serotonergic neurons in the raphe area as revealed by the equal number of serotonergic neurons in the dorsal raphe in all three genotypes.
Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus.
In this study, in-vivo recordings of serotonergic dorsal raphe neurons were performed in the anesthetized rat, whereas tobacco extracts, cigarette smoke extracts, nicotine, nornicotine or anabasine were intravenously injected.
The stress circuit runs from the hippocampus to the amygdala to the dorsal raphe nucleus to the entorhinal cortex and back to the hippocampus. New therapeutic ideas for decreasing seizure frequency in TLE include the use of anti-depressants, ethosuximide (which blocks firing in the dorsal raphe nucleus), and mood-stabilizers (which block firing in the entorhinal cortex).
It is thus little surprising when the neuropeptide, galanin, is discovered to coexist with norepinephrine (NE) in locus coeruleus (LC) neurons and with serotonin (5-HT) in the dorsal raphe nucleus (DRN) neurons, a link between galanin mediated signaling and mood regulation is sought.
Here, we used extracellular single unit recording in midbrain slices to examine glutamate receptor mediated effects on 5-HT neuronal activity in the dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN).
It is well known that the dorsal raphe nucleus (DRN) sends serotonergic and nonserotonergic projections to target regions in the brain stem and forebrain, including the vestibular nuclei.
This may involve interactions within the circuitry controlling 5-HT neurons in the dorsal raphe nucleus (DRN) that project to the nucleus accumbens (NAcc).
Serotonergic fibers originate from the dorsal raphe nuclei (DRN), noradrenergic fibers from the locus coeruleus (LC).
After intravenous infusions to steady-state levels in plasma, 6-OH-buspirone and buspirone increased 5-hydroxytryptamine (HT)(1A) receptor occupancy in a concentration-dependent manner with EC(50) values of 1.0 +/- 0.3 and 0.38 +/- 0.06 microM in the dorsal raphe and 4.0 +/- 0.6 and 1.5 +/- 0.3 microM in the hippocampus, respectively. Both compounds appeared to be approximately 4-fold more potent in occupying presynaptic 5-HT(1A) receptors in the dorsal raphe than the postsynaptic receptors in the hippocampus.
5-HT immunoreactivity in the dorsal raphe nucleus and the median raphe nucleus was also similarly detected in both animal groups.
We investigated age-related changes in learning and memory performance and behavioural extinction in the water maze; and in endogenous levels of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the neocortex, hippocampus, thalamus and dorsal raphe nucleus of Wistar rats. An age-dependent decrease in 5-HIAA levels was observed in both hippocampus and dorsal raphe nucleus (DRN).
Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input.
The dorsal raphe nucleus (DRN) of brain stem is the main source of serotonergic innervation of limbic structures fundamental in the regulation of emotionally influenced behavior.
Hippocampal function is modulated by serotonergic projections mostly from dorsal raphe nucleus in the midbrain.
In the second experiment, the 5-HT(1B) agonist CP-93,129 (0-1.0 microg) was microinjected into the dorsal raphe 10 min before the FI 10 schedule. CONCLUSIONS: These data extend the anti-aggressive effects of 5-HT(1B) agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT(1B) receptors in the dorsal raphe..
In the present study, changes in the neuronal activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT(1A) receptor antagonist WAY-100635 in a rat model of Parkinsonos disease (PD) were investigated by using extracellular single unit recording.
Specifically, estradiol-17beta in its acute positive feedback mode for gonadotropin release in the female rat induces expression of the genes for the 5-hydroxytryptamine(2A) receptor (5-HT(2A)R) and the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN).
The highest labeling was observed in monoaminergic neuron regions (caudate putamen, olfactory tubercle, nucleus accumbens, substantia nigra, dorsal raphe and locus coerules).
Serotonergic innervation of the cortex arises predominantly from the dorsal raphe nucleus (DRN). RESULTS: dorsal raphe nucleus neuron number (controls: 80,386+/-10,238; alcoholic individuals: 85,884+/-12,478) was not different between groups but TPH-IR was greater in alcoholic individuals throughout the rostrocaudal extent of the DRN.
The hypothesis is as follows: There is a basic circuit of emotion which runs from the hippocampus (defined as the dentate gyrus plus the CA regions), where emotion arises, to the amygdala and from there to serotonergic pacemaker cells in the dorsal raphe nucleus (DRN).
The subthalamic nucleus receives serotonergic projections from the dorsal raphe nucleus. The aim of the present work is to study the changes in the firing of subthalamic neurons in rats with 5,7-dihydroxytryptamine lesions of the dorsal raphe nucleus and rats with combined 5,7-dihydroxytryptamine lesions in the dorsal raphe nucleus and 6-hydroxydopamine lesions in the substantia nigra pars compacta by using single-unit extracellular recordings. In rats with 5,7-dihydroxytryptamine lesions of the dorsal raphe nucleus, the firing rate of subthalamic neurons increased significantly compared with normal rats and the firing pattern changed significantly towards a more bursting firing in the majority of the neurons observed. In rats with combined dorsal raphe nucleus and substantia nigra pars compacta lesions, the firing rate and firing pattern of subthalamic neurons did not show a significant difference compared to rats with lesions of the substantia nigra pars compacta. However, dorsal raphe nucleus and substantia nigra pars compacta lesions combined increased significantly the percentage of subthalamic neurons with burst-firing pattern compared to normal rats, while having no effect on their firing rate. These results show that the serotonergic efferent projections of the dorsal raphe nucleus significantly influence on the activity of subthalamic neurons and that the loss of dopaminergic projection by substantia nigra pars compacta lesion decreases the effect of the lesions of the dorsal raphe nucleus on subthalamic nucleus neuronal activity, suggesting that the role of the dorsal raphe nucleus may be exerted by the dorsal raphe nucleus-substantia nigra pars compacta-subthalamic nucleus pathway..
Subcortically, the medial septum, nucleus of the diagonal band, supramammillary nucleus, lateral hypothalamus, dorsal raphe nucleus, and the thalamic nucleus reuniens all send projections through the fornix, which presumably terminate in the hippocampus and adjacent parahippocampal region.
We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c.
The aim of the present studies was to investigate the effect of CART peptides on extracellular 5-HT in the dorsal raphe nucleus (DRN) and nucleus accumbens (NAcc) using a microdialysis approach in freely behaving rats.
We additionally found out that, compared to controls, c-Fos immunoreactivity in hypothalamus and dorsal raphe nucleus was increased in rats that received URB597, oleoylethanolamide or palmitoylethanolamide (10, 20 microg/5 microl, i.c.v.).
Because rats learn to lever-press for brief electrical stimulation of the median and dorsal raphe nuclei (MRN and DRN, respectively), these brain sites have long been implicated in reward processes. The present results suggest that median and dorsal raphe neurons presumably inhibited by muscimol via GABA(A) receptors are involved in integration of primary reinforcement, and that median raphe neurons exert tonic inhibition over dopamine-dependent reward circuitry.
In a non-stressed menstrual cycle, SS animals have lower levels of estrogen and progesterone, lower activity of the serotonin system and lower expression of genes related to the serotonin system in the dorsal raphe nucleus.
The goal of the present study was to identify the projection from the subdivisions of the amygdaloid nuclear complex to specified subregions of the dorsal raphe (DR) nucleus and to attempt to compare the density of amygdaloid input to the DR with that of inputs from other limbic structures.
Furthermore, when 5-HTnergic neuronal function was examined using antibodies against tryptophan hydroxylase (TPH) following the behavioral tests, fluvoxamine significantly reversed the loss of TPH-positive cells produced by OBX in the dorsal raphe.
The present study investigated the stimulatory effect of the MS extract on the dorsal raphe nucleus and its antidepressant-like activity. The stimulatory effect of the MS extract was determined by detecting the expression of the immediate early gene, cfos, in the dorsal raphe nucleus of male Wistar rats. These findings indicate that the MS extract has a stimulatory effect on the dorsal raphe nucleus and an antidepressant-like activity. These findings suggest that the MS extract might produce antinociceptive and/or antidepressive actions partly through activation of the dorsal raphe nucleus. Moreover, the dorsal raphe nucleus may be one of site of MS action in the central nervous system..
Over a hundred years ago, Santiago Ramón y Cajal used a new staining method developed by Camillo Golgi to visualize, among many other structures, what we today call the dorsal raphe nucleus (DRN) of the midbrain.
Serotonergic systems arising from the mid-rostrocaudal and caudal dorsal raphe nucleus (DR) have been implicated in the facilitation of anxiety-related behavioral responses to anxiogenic drugs or aversive stimuli.
Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT(7) receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection.
OBJECTIVE: To investigate the efferent pathway from the dorsal raphe nucleus to the inner ear. The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunfluorescence technique after a survival period of 7 days. RESULTS: (1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB-labelled neurons were densely distributed in a dorsomedian part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN.
Our data suggests that fMRI activity in the hypothalamus, the dorsal raphe nucleus, the periaqueductal gray, and the rostroventral medulla showed significant correlation with LF/HF ratio calculated from simultaneous HRV data.
The VTA and SNc cells have efferent and afferent connections with the dorsal raphe nucleus (DRN), the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT), the locus coeruleus (LC), the lateral and posterior hypothalamus (LH), the basal forebrain (BFB), and the thalamus.
The RLi also sends substantial projections to the magnocellular preoptic nucleus, lateral hypothalamus, central division of the mediodorsal thalamic nucleus, lateral part of the lateral habenula and supraoculomotor region, and light projections to the prefrontal cortex, basolateral amygdala, and dorsal raphe nucleus.
It is well known that dorsal raphe nucleus (DRN) is one of the key structures for the development of opioid analgesia and tolerance.
In vivo electrophysiology in the rat dorsal raphe and microdialysis in freely moving guinea pigs and rats were used to evaluate the functional outcome of SB-649915-B.
RESULTS: The systemic administration of aripiprazole reduced 5-HT output in the medial prefrontal cortex (mPFC) and dorsal raphe nucleus of the rat.
The increase of 5-HT in the striatum was reversed by systemic and by local administration of the benzodiazepine antagonist flumazenil in the dorsal raphe nucleus by a microdialysis probe, suggesting that the increase in 5-HT was mediated by the activity of ELB139 at the benzodiazepine binding site. As the dorsal raphe nucleus is rich in alpha-3 subunits, this effect of ELB139 may be mediated by its subtype selectivity.
In in vivo electrophysiology studies, aripiprazole produced a dose-related reduction in the firing rate of 5-HT-containing dorsal raphe neurons in rats, which was both prevented and reversed by WAY-100635 administration.
RESULTS: The ILL AN women had a highly significant (30%-70%) increase in [ 11C]WAY100635 BP in prefrontal and lateral orbital frontal regions, mesial and lateral temporal lobes, parietal cortex, and dorsal raphe nuclei compared with CW.
HCRT neurons receive serotonergic afferents from the dorsal raphe nucleus.
Of ten dorsal raphe nucleus (DRN) neurons firing short stereotyped bursts within an otherwise regular firing pattern, all exhibited immunoreactivity for either 5-HT (n = 6) or the 5-HT synthesizing enzyme, tryptophan hydroxylase (TRH; n = 2) or both (n = 2).
LE-rats had significantly higher levels of oxidative metabolism in dorsal raphe and inferior colliculi.
In the LMS females tissue levels of both 5-HT and 5-hydroxyindole acetic acid (5-HIAA) were significantly increased in the dorsal raphe nucleus, and 5-HIAA and homovanillic acid levels were also elevated in the nucleus accumbens as compared with AFR and BMS rats.
Newborn male offspring (Bis-A mice) were evaluated for the immunoreactivity of ERs alpha and beta, serotonin, and serotonin transporter positive cells in the dorsal raphe nucleus (DRN).
The connections of trigeminal nucleus with the locus coeruleus and dorsal raphe nucleus may account for the observed phenotypic differences between the two groups.
Serotonin (5-HT)-containing neurons in the dorsal raphe project to the external and internal segments of the pallidum, which express several 5-HT receptors.
Additional experiments found that the initial experience with control blocks the intense activation of serotonergic cells in the dorsal raphe nucleus that would normally be produced by uncontrollable stress, providing a mechanism for behavioral immunization.
Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. These findings demonstrate that in the dorsal raphe nucleus of chronically stressed rats, citalopram normalizes TPH expression and blocks stress effects on distinct genes related to neurotransmitter release and neuroplasticity..
Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome..
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