Raphe Nuclei

In all vertebrates, prominent serotonergic neurons are found in the superior and inferior Raphe nuclei in the hindbrain innervating most CNS regions.  

ANOVA of 5-HT(1A) receptor availability demonstrated a significant effect of MAO-A genotype in the Raphe nuclei, medial and inferior temporal cortex, insula, medial prefrontal cortex, and anterior cingulate (p < 0.05).  

Treatment effects on c-Fos expression in serotonergic and non-serotonergic cells in the midbrain Raphe nuclei were determined 2 h following open-field exposure or home cage control (CO) conditions. Rats tested under both light conditions responded with increases in c-Fos expression in serotonergic neurons within subdivisions of the midbrain Raphe nuclei compared with CO rats.  

The brainstem Raphe nuclei are typically assigned a role in serotonergic brain function.  

Five general brain regions contained retrogradely labeled neurons: cerebral cortex (infralimbic and insular regions), rostral forebrain structures (subfornical organ, organum vasculosum of the lamina terminalis, taenia tecta, nucleus accumbens, lateral septum, endopiriform nucleus, dorsal BST, substantia innominata, and, most prominently the amygdala--primarily its basomedial and central subnuclei), thalamus (central medial, intermediodorsal, reuniens, and, most prominently the paraventricular thalamic nucleus), hypothalamus (medial preoptic area, perifornical, arcuate, dorsomedial, parasubthalamic, and posterior hypothalamic nuclei), and brainstem (periaqueductal gray matter, dorsal and central superior Raphe nuclei, parabrachial nucleus, pre-locus coeruleus region, NTS, and A1 noradrenergic neurons in the caudal ventrolateral medulla).  

Multimodal MR images can directly or indirectly help in identifying the substantia nigra, locus ceruleus, and Raphe nuclei that contain monoamine neurons.  

slc6a4a and slc6a4b are expressed in the Raphe nuclei, retina, medulla oblongata, paraventricular organ, pretectal diencephalic complex, and caudal zone of the periventricular hypothalamus, in line with the expression profiles of homologues from other vertebrates.  

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.  

These regions include the Raphe nuclei, pontine nuclei, and rostral ventrolateral medulla.  

Dual-infected neurons were detected in the ventrolateral medulla, nucleus of the solitary tract, caudal Raphe nuclei, A5 cell group, and hypothalamic paraventricular nucleus.  

We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and Raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion).  

The bulk of neuroanatomical data available clearly indicate that DA-containing neurons in the brain receive a prominent innervation from 5-HT originating in the Raphe nuclei of the brainstem. Furthermore, this modulation seems to be reciprocal; DA neurons innervate the Raphe nuclei and exert a tonic excitatory effect on them.  

The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [ (18)F]MPPF BP in the Raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [ (18)F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the Raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus.  

Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, locus coeruleus, ventral subcoeruleus nucleus, and Raphe nuclei.  

Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and Raphe nuclei.  

PURPOSE: Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [ (18)F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in different regions of animal and human brain, including that of 5-HT(1A) autoreceptors in the Raphe nuclei. RESULTS: Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), Raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and Raphe nuclei.  

Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the Raphe nuclei..  

Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the Raphe nuclei of the brainstem, resulting in a near-complete loss of 5-HT throughout the brain.  

5-HT(1A), 5-HT(4) and 5-HT(6) receptors are densely expressed in brain regions innervated by serotonergic projections from the Raphe nuclei and are associated with learning and memory.  

Whereas the entorhinal cortex (EC) receives profuse serotonergic innervations from the Raphe nuclei in the brain stem and is critically involved in the generation of temporal lobe epilepsy, the function of serotonin (5-hydroxytryptamine, 5-HT) in the EC and particularly its roles in temporal lobe epilepsy are still elusive.  

In this study, we established rat organotypic mesencephalic slice cultures containing the Raphe nuclei and examined the effects of sustained exposure to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH).  

However, the role of these three Raphe nuclei in the acupuncture responses is unknown. In baroreceptor denervated and vagotomized cats, the present study evaluated c-Fos activation in the Raphe nuclei induced by EA and examined its relationship to enkephalin and 5-HT. Perikarya containing the opioid and 5-HT were found in the Raphe nuclei of all animals following application of colchicine. These results suggest that the medullary Raphe nuclei, particularly the NRP, process somatic signals during EA and participate in EA-related modulation of cardiovascular function through an opioid or serotonergic mechanism..  

Midbrain slices containing the dorsal and medial Raphe nuclei were prepared from rat brain, loaded with [ (3)H]serotonin ([ (3)H]5-HT), superfused and the release of [ (3)H]5-HT was determined at rest and in response to electrical stimulation. Manipulation of 5-HT transporter function modulates extracellular 5-HT concentrations in the Raphe nuclei: of the SSRIs, fluoxetine was found 5-HT releaser, whereas citalopram did not exhibit this effect. Serotonergic projection neurons in the Raphe nuclei possess inhibitory 5-HT(1A) and 5-HT(1B/1D) receptors and facilitatory 5-HT(3) receptors, which regulate 5-HT release in an opposing fashion. This observation indicates that somatodendritic 5-HT release in the Raphe nuclei is under the control of several 5-HT homoreceptors. Evidence was found for reciprocal interactions between serotonergic and glutamatergic as well as serotonergic and GABAergic innervations in the Raphe nuclei. Serotonergic neurons in the Raphe nuclei also receive noradrenergic innervation arising from the locus coeruleus and alpha-1 and alpha-2 adrenoceptors inhibited [ (3)H]5-HT release in our experimental conditions.  

Volumes of interest (VOIs) selected a priori included: anterior cingulate cortex (ACC), anterior insula, hippocampus, amygdala, thalamus, hypothalamus and midbrain Raphe nuclei.  

Further evidence for CB(1) involvement in hamster circadian rhythms was provided by immunohistochemical detection of CB(1) receptors in four separate nuclei comprising the principal components of the hamster circadian system: the suprachiasmatic nucleus, intergeniculate leaflet of the thalamus, and dorsal and median Raphe nuclei.  

However, neuropathological differences were absent in the dorsal Raphe nuclei, amygdala, and cortical regions.  

INTRODUCTION: Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the Raphe nuclei, together with brain growth retardation. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral Raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections).  

During the first 2 weeks of postnatal development, numerous GATA3-expressing cells were found in the intergeniculate leaf, ventral lateral geniculate nucleus, pretectal nucleus, nucleus of the posterior commissure, superior colliculus, inferior colliculus, periaqueductal grey, substantia nigra and Raphe nuclei.  

Here, the possibility that 5-HT-1A-mediated feedback inhibition of the Raphe nuclei is topographically organized was examined.  

In the hindbrain, Lmx1b-expressing neurons were primarily observed in the Raphe nuclei, parabrachial nuclei, principal sensory trigeminal nucleus, nucleus of the solitary tract, and laminae I-II of the medullary dorsal horn as well as spinal dorsal horn.  

Two hours of darkness at mid-subjective day (circadian time 6; CT-6) resulted in increased concentrations of 5-HT in the SCN tissue and induction of c-FOS expression in the Raphe nuclei.  

For example, 5-HT1A receptor agonists produced anxiolytic-like effects in the Raphe nuclei, but inconsistent effects in the amygdala, septum, and hippocampus. Conversely, 5-HT3 receptor antagonists produced anxiolytic-like effects in the amygdala but not in the Raphe nuclei.  

In this study we examine the role of the rostral ventromedial medulla (RVM), which includes Raphe nuclei pallidus and magnus, in the expression of these changes.  

A retrograde neural tracer, Fluoro-Gold (FG), was infused into the right side of these regions in ovariectomized rats and the numbers of FG and/or 5-HT immunopositive cells in the right and left sides of the Raphe nuclei were counted. Thus, laterality of the projections is thought to be strong in the 5-HT clusters located far from the midline of the midbrain Raphe nuclei..  

In addition to MCH+ axons, we found MCH-immunoreactive cells that have not been previously described either in the midbrain Raphe nuclei or in the periaqueductal and periventricular areas. cells in subventricular regions and the midbrain Raphe nuclei. The MCH+ cells in the midbrain Raphe nuclei were closely related to neuronal processes of serotonergic neurons. We conclude that MCH is present in tanycytes whose processes innervate the midbrain Raphe nuclei and adjacent subependymal regions.  

The results imply that blockade of the 5-HT1A receptors in the forebrain will counteract the favourable (antidepressant-like) effect at Raphe nuclei level, and consequently, the overall effect evidenced is an antagonism. In contrast, the antinociceptive effect of venlafaxine is probably potentiated due to the blockade of somatodendritic 5-HT1A receptors in the same Raphe nuclei, facilitating the descending monoaminergic pain control system..  

The suprachiasmatic nucleus of the hypothalamus receives dense serotonergic projections from the Raphe nuclei.  

Lower but distinct GR-ir was observed in the internal granule cell layer of the olfactory bulbs, dorsal and lateral pallium, striatum, various subfields of the amygdala, bed nucleus of the stria terminalis (BNST), optic tectum, various tegmental nuclei, locus coeruleus, Raphe nuclei, reticular nuclei, and the nuclei of the trigeminal motor nerves.  

Tryptophan restriction was also associated with a reduction of serotonin immunoreactive cells in the Raphe nuclei and increased cAMP levels in the superior colliculus.  

Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of the solitary tract, caudal Raphe nuclei, A5 cell group, hypothalamic paraventricular nucleus) from the left adrenal was more severe than that from the right organ.  

We have recently described a discrete region of the medullary Raphe nuclei, termed the midline apneic site (MAS) that produces profound apnea upon chemical stimulation. 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; K├Âlliker-Fuse nucleus; intertrigeminal region; rostral ventrolateral medulla; lateral parafacial region; and the ventral respiratory group.  

Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-Raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats.  

Therefore tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin in the Raphe nuclei could be a candidate.  

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.  

0.5 M sodium lactate or saline, in control and panic-prone rats on c-Fos expression in serotonergic neurons within subdivisions of the midbrain/pontine Raphe nuclei.  

5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal Raphe nuclei, in both males and females.  

To analyze the differential recruitment of the Raphe nuclei during different phases of feeding behavior, rats were subjected to a food restriction schedule (food for 2 h/day, during 15 days). Additional experiments revealed few double-labeled (FOS-IR+5-HT-IR) cells within the Raphe nuclei in the MFI group, suggesting little serotonergic activation in the raphe during food ingestion. These findings suggest a differential recruitment of Raphe nuclei during various phases of feeding behavior.  

Transient increases followed by decreases were detected in 5-HTT mRNA expression of dorsal and median Raphe nuclei at 7d after the treatment.  

Although virtually all of serotonin (5-HT) neurons in the midbrain Raphe nuclei of rats are known to express vesicular glutamate transporter 3 (VGLUT3), VGLUT3-positive 5-HT fibers have been identified only in the cerebral cortex and hippocampus.  

CARTp-immunoreactive cells occur in the olfactory bulb, nucleus accumbens, amygdala, septum, striatum, nucleus of Bellonci, ventrolateral nucleus, central thalamic nucleus, preoptic nuclei, and suprachiasmatic nucleus, and particularly in the medial pallium, ventromedial nucleus, hypothalamus, Edinger-Westphal nucleus, optic tectum, Raphe nuclei, central gray, nucleus of the solitary tract, and spinal cord.  

In addition, recent studies suggest that the serotonergic neurons from the Raphe nuclei to limbic areas modulate the mesocorticolimbic dopaminergic-glutamatergic system and participate in the neuropsychotoxicity.  

In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the Raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression.  

The ascending serotonergic projections from the Raphe nuclei restrain and control the function of these loops.  

We found that these PT neurons and two other GFP labeled non-TH type neuronal groups, one in the paraventricular organ of the posterior tuberculum and the other in the hypothalamus, were significantly reduced after exposure to MPTP, while the rest of GFP-positive neuronal clusters, including those in telencephalon, pretectum, Raphe nuclei and locus coeruleus, remain largely unchanged.  

We conclude that (1) RTN receives input from multiple Raphe nuclei, (2) serotonin, substance P, and TRH activate RTN chemoreceptors, and (3) excitatory effects of serotonin and pH are mediated by distinct ionic conductances.  

We determined the prevalence of neurons that retrogradely label with both tracers in the constituent nuclei of the rostromedial medulla, the Raphe nuclei, the gigantocellular reticular nucleus (Gi, bilaterally), the Gi pars alpha (GiA, bilaterally), and the midline medullary reticular formation. A large fraction of neurons in each of these nuclei had bulbospinal projections, ranging from > or =56% for the Raphe nuclei to > or =14% for the Gi.  

Anatomical and neurochemical studies indicated that the globus pallidus receives serotonergic innervation from Raphe nuclei but the membrane effects of 5-HT on globus pallidus neurons are not entirely clear.  

Possible connections between the retina and the Raphe nuclei were investigated in the monkey Cebus apella by intraocular injection of cholera toxin B subunit (CTb).  

The effect of CRF on behavior and on the accompanying change in activity of 5-HT neurons in the dorsal and median Raphe nuclei (DR and MR) that project to the ventral medial prefrontal cortex (mPFC), a brain area implicated in mood and anxiety disorders, was studied.  

Enhanced cough FLI was found bilaterally at following brainstem structures, as compared to controls: In the medulla, FLI was increased in the medial, interstitial and ventrolateral subnuclei of the solitary tract (p < 0.02), in the retroambigual nucleus of the caudal medulla (p < 0.05), in the ambigual, paraambigual and retrofacial nuclei of the rostral medulla along with the lateral reticular nuclei, the ventrolateral reticular tegmental field (p < 0.05), and the Raphe nuclei (p < 0.05).  

The physiological effects of emotions are mediated to autonomic nervous system by the hypothalamus, also innervated by the serotonergic Raphe nuclei.  

Raphe nuclei, which modulate several physiological functions through serotonin, receive dense projections from orexin-containing neurons in the hypothalamus.  

Interestingly, we did not detect NgR1-3 mRNAs in monoaminergic neurons in the substantia nigra, ventral tegmental area, locus caeruleus, and Raphe nuclei, which are known to have high regenerative capacity.  

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).  

For example, exposure to cold can activate components of the reticular activating system such as Raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons.  

We determined monoamine (metabolite) tissue levels in the medial prefrontal cortex, orbitofrontal cortex, lateral hypothalamus, Raphe nuclei and cerebrospinal fluid, and found that the 5-HT levels, but not other monoamine tissue levels, were reduced in SERT( -/-) rats.  

Manganese habenula injection revealed enhanced interpeduncular (IP) and Raphe nuclei signals of the 6-OHDA rat group.  

We used the RN46A-B14 cell line, derived from rat embryonic Raphe nuclei.  

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.  

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. 5-HT TISSUE CONTENT AND 5-HT TURNOVER IN THE TISSUE: Compared to controls, WAY 100635, GR127935 and the combination thereof, decreased cortical 5-HT (-30%), increased 5-HIAA and consequently 5-HT turnover in the cortex threefold and the Raphe nuclei twofold.  

The binding potential (BP) was calculated for Raphe nuclei, hippocampus and frontal cortex. RESULTS: In all regions, the BP for both [ 11C]WAY 100635 (Raphe nuclei 1.85-4.71, hippocampus 2.52-6.17, frontal cortex 2.03-3.79) and [ 11C]MADAM (2.70-7.65, 0.47-1.76, 0.18-0.51) varied several fold between subjects. In the Raphe nuclei, where the two markers are situated on the same neurons, the ratio of [ 11C]WAY 100635 binding to [ 11C]MADAM BP binding varied considerably (0.43-1.05). There was a positive correlation between the two markers in the Raphe nuclei (rxy=0.68, p<0.05) and in the hippocampus (rxy=0.97, p<0.001) but not in the frontal cortex (rxy=-0.25, p=0.44). CONCLUSIONS: The results support a correlation between density levels of the 5-HT1A-receptor and the 5-HTT in the Raphe nuclei and hippocampus but not in the frontal cortex.  

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter and tryptophan hydroxylase (TPH) catalyzes the rate-f the Raphe nuclei.  

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.  

Immunoreactive perikarya were observed within sensory and motor nuclei of cranial nerves, dorsal column nuclei, olivary nuclear complex, reticular formation, pontine nuclei, locus caeruleus, Raphe nuclei, substantia nigra, and quadrigeminal plate.  

In mice killed 24 h later (3 d after injection), GFP-expressing cells were identified (in order of density) in the Raphe nuclei, periaqueductal grey, locus coeruleus, nucleus tractus solitarius, and area postrema.  

The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine Raphe nuclei.  

A low tryptophan diet led to decreases in plasma tryptophan levels, low ratio of tryptophan/large neutral amino acid, whole blood 5-HT, and neuronal 5-HT content in the Dorsal and Median Raphe nuclei, as well as altered c-fos expression in the brain.  

This finding serves further evidence that glutamate released from axon terminals of the cortico-striatal projection neurons stimulates serotonergic neurons in the Raphe nuclei and this effect is mediated at least in part by postsynaptic NMDA receptors.  

Maps of receptor availability were generated from the images of eight cortical regions and Raphe nuclei. RESULTS: The maps showed highest binding in limbic areas and Raphe nuclei, while binding in basal ganglia and cerebellum was negligible.  

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.  

Serotonergic neurons originating in the Raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia.  

The highest levels of Spd synthase expression were detected in the accumbens nucleus, taenia tecta, cerebellar cortex, cerebral cortical layer I, hippocampus, hypothalamus, mesencephalic Raphe nuclei, central and lateral amygdala, and the circumventricular organs.  

Immunohistochemical studies revealed nesfatin-1-immunoreactive (irNEF) cells in the Edinger-Westphal nucleus, dorsal motor nucleus of vagus, and caudal Raphe nuclei of the rats, in addition to the hypothalamus and NTS reported in the initial study.  

TPH2 immunoreactivity (IR) was detected throughout the Raphe nuclei, in lateral hypothalamic nuclei and in the pineal body of rodent and human brain. We recently reported that glucocorticoid treatment of C57/Bl6 mice for 4 days markedly decreased TPH2 messenger RNA levels in the Raphe nuclei, whereas TPH1 mRNA was unaffected.  

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.  

In the rhombencephalon, cells were found in the cerebellum, the reticular formation, the locus coeruleus, the Raphe nuclei, and the nuclei of the cranial nerves.  

Enhanced voluntary locomotor activity during 6 wk increased the level of Tph2 mRNA in both Raphe nuclei of control rats without concomitant increase of corticosterone plasma levels.  

The present study was carried out to assess the influence of noradrenergic stimulation of the midbrain dorsal (DRN) and median Raphe nuclei (MRN) on urinary volume and electrolyte excretion in hydrated rats.  

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. There was also a significant increase of the 5-HT turnover in MS2-15 animals in the Raphe nuclei, mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA) levels, and an increase of 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ventral tegmental area (VTA) of stressed females.  

However, there was no significant influence on the 5-HT synthesis rate in the dorsal and median Raphe nuclei and the majority of their projection areas.  

METHODS: The functional relevance of TPH2 promoter polymorphisms was determined with luciferase assays in primary serotonergic neurons from rat Raphe nuclei and in human small cell lung carcinoma cells (SHP-77 cells).  

Serotonin (5-HT) and the dorsal Raphe nuclei (DRN) have been implicated in the inhibitory control of salt intake (i.e., sodium appetite).  

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