Disease relevance of Raphe Nuclei

• After the development of hypertension, a significant decrease of ANF could be detected in four more brain areas (bed nucleus of the stria terminalis, paraventricular and arcuate nuclei, dorsal raphe nucleus) of SHR, as compared with normotensive controls, and the increase in the median eminence was no longer detectable [1].
• Injections of 5,7-dihydroxytryptamine (5,7-DHT) in the dorsal and medial raphe nuclei, producing a partial loss of 5-HT neurons, induced rapid and transient increases in glial fibrillary acidic protein immunoreactivity indicative of a reactive gliosis, but no changes in the S100beta or tenascin-C normally secreted by astroglial cells [2].
• 8-Hydroxy-2-(di-n-propylamino) tetralin, a selective serotonin1A receptor agonist, blocks haloperidol-induced catalepsy by an action on raphe nuclei medianus and dorsalis [3].
• Further, like 8-OH-DPAT, LY 165,163 acted as an agonist in inhibiting the firing of dorsal raphé nucleus neurons, in reducing striatal turnover of 5-HT and in eliciting both hypothermia and corticosterone secretion [4].
• In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine [5].

Psychiatry related information on Raphe Nuclei

• Similar infusions of BDNF into the dorsal raphe nucleus produce an antidepressant effect, as evaluated by several 'learned helplessness' paradigms [6].
• The purpose of this study was to determine the roles of the presynaptic 5-hydroxtryptamine1A (5-HT1A) receptors in the median raphé nucleus (MRN) and of the postsynaptic 5-HT1A receptors in its projection area of the dorsal hippocampus in the social interaction and elevated plus-maze tests of anxiety [7].
• One week after a single social defeat stress, cross-sensitization to cocaine is evident in terms of enhanced motor activity as well as in terms of increased Fos labeling in the periaqueductal grey area, the locus coeruleus, and the dorsal raphe nuclei [8].
• We performed a quantitative immunohistochemical study of serotonin (5-HT)-containing neurons linked to hypersomnia in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) in 8 patients with MyD, 5 of whom showed hypersomnia, and in 12 age-matched controls [9].
• In animals, sleep deprivation and pharmacologic treatment with antidepressants exert similar effects on 5-HT neurotransmission, notably functional desensitization of 5-HT1A autoreceptors located on 5-HT neurons in the dorsal raphe nucleus (DRN) [10].

High impact information on Raphe Nuclei

• We present here electrophysiological evidence for decreased postsynaptic sensitivity to GABA following chronic benzodiazepine administration as measured by the direct iontophoretic application of GABA and serotonin onto serotonergic cells in the midbrain dorsal raphe nucleus (DRN), known to receive GABAergic input [11].
• Injecting radioactive transmitters into the rat substantia nigra led to retrograde neuronal labeling either in the dorsal raphe nucleus, after 3H-labeled serotonin injection, or in the caudoputamen, after 3H-labeled gamma-aminobutyric acid injection [12].
• In addition, MDMA produced pathological changes in nerve cell bodies in the dorsal, but not median, raphe nucleus [13].
• Neuropeptide Y might be quite important in the regulation of neuronal state, as exemplified by its actions in the hippocampus and the dorsal raphé nucleus [14].
• CRF-containing neurons projecting from the paraventricular nucleus to the median eminence, which are involved in controlling pituitary-adrenocortical function, receive synaptic input from serotonin neurons projecting from the midbrain raphe nuclei [15].

Chemical compound and disease context of Raphe Nuclei

• In contrast, activation of somatodendritc 5-HT(1A) receptors in the raphe nuclei reduces forebrain 5-HT bioavailability and agonists of these receptors, including 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), reliably stimulate eating behavior [16].
• The effects of pharmacological challenges to the benzodiazepine receptors in the dorsal hippocampus and median raphé nucleus were investigated in the social interaction and the elevated plus-maze tests of anxiety in rats [17].
• Recording the electrophysiological activity of 5-HT neurons in the nucleus raphe dorsalis (NRD) revealed that both chronic treatment with zimelidine and REM sleep deprivation induced a hyporeactivity of these neurons to the inhibitory effect of citalopram in "normal" rats [18].
• It is concluded that low doses of d-amphetamine can reduce locomotor activity and that the effects may be mediated via an enhancement of the release of 5-hydroxytryptamine from the system arising in the median raphe nucleus [19].
• However, 8-OHDPAT and BMY-7378 were found to increase or decrease motor activity, after injection into the median or dorsal raphe nuclei, respectively [20].

Biological context of Raphe Nuclei

• Auditory evoked potentials reflect serotonergic neuronal activity--a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus [21].
• Finally, a high density of [3H]flunitrazepam binding sites was found in the dorsal (and the median) raphé nucleus, the Kd and Bmax values being not altered by prior infusion of 5,7-dihydroxytryptamine [22].
• The effect of median raphe nucleus lesion on turnover of acetylcholine in the hypothalamus is most likely unrelated to regulation of blood pressure [23].
• 4. Gepirone (0.2 micrograms) and ipsapirone (0.04 and 0.2 micrograms) increased food intake when injected into the dorsal raphé nucleus (DRN), presumably by inhibiting the activity of DRN 5-hydroxytryptaminergic afferents [24].
• PCA and MDMA excitations of startle were attenuated in rats specifically depleted of spinal 5-HT or in rats with radio frequency lesions of the dorsal raphe nucleus [25].

Anatomical context of Raphe Nuclei

• PLC-A mRNA was highest in the mitral cell layer of the olfactory bulb, choroid plexus, hippocampus and dentate gyrus, magnocellular hypothalamic nuclei, rostral raphe nuclei, and cerebellar Purkinje cells [26].
• (6) Because almost all the serotoninergic fibers in the spinal cord originated from the brain stem raphe nuclei, propriospinal serotonin positive cells were considered as phylogenetic vestiges [27].
• (3) By E8 the number of serotonin positive cells in the brain stem increased, and virtually all the raphe nuclei found in an adult animal were located [27].
• Pharmacology and distribution of norepinephrine transporters in the human locus coeruleus and raphe nuclei [28].
• Moderate levels of CRF2 receptor expression were evident in the olfactory bulb, amygdaloid nuclei, the paraventricular and suraoptic nuclei of the hypothalamus, the inferior colliculus and 5-HT-associated raphe nuclei of the midbrain [29].

Associations of Raphe Nuclei with chemical compounds

• Tryptophan hydroxylase [EC 1.14.16.4; L-tryptophan, tetrahydropteridine:oxygen oxidoreductase (5-hydroxylating)], the enzyme catalyzing the rate-limiting step in the biosynthesis of serotonin, was purified 79-fold from the region of the raphe nucleus of rat midbrain by sequential column chromatography and disc-gel electrophoresis [30].
• There may exist a rostrally projecting neuronal tryptamine containing system arising from cell bodies in or close to the nucleus raphé medianus [31].
• The disappearance of the hybridization signal for GAP-43 mRNA after intracerebroventricular injections of the neurotoxins 5,7-dihydroxytryptamine (5,7-DHT) or 6-hydroxydopamine (6-OHDA) indicated that high levels of GAP-43 are synthesized in the serotonergic neurons of the raphe nuclei and in the catecholaminergic neurons of the SNc, VTA, and LC [32].
• Morphological evidence demonstrates the existence of dopaminergic afferent pathways and dopamine (DA)-containing neurons in the dorsal raphe nucleus (DRN) [33].
• Levels of mRNA for the SERT in the raphe nucleus were also unaltered by chronic paroxetine treatment [34].

Gene context of Raphe Nuclei

• Differential hormonal regulation of tryptophan hydroxylase-2 mRNA in the murine dorsal raphe nucleus [35].
• Previously, we reported elevated levels of TPH protein in the dorsal raphe nucleus (DRN) of depressed suicides and now examine expression of neuronal TPH2 mRNA in a cohort of matched controls and depressed suicides (n = 11 pairs) [36].
• For example, CRH is contained in a number of central neural systems that can influence behavior, including limbic areas, the hypothalamus, locus coeruleus, median raphé nuclei, and cortical interneurons [37].
• Galanin mRNA-producing neurones were limited to the dorsal raphe nucleus and to a second population in the ventral border of the aqueduct [38].
• 1. The effect of bath application of sulphated cholecystokinin octapeptide (CCK-8) was studied on neurones in slices containing rat raphe nucleus [39].

Analytical, diagnostic and therapeutic context of Raphe Nuclei

• Immunocytochemistry performed on rat brain sections with CT-2 antibody revealed SERT expression associated with brainstem raphe nuclei in a pattern virtually identical to that obtained by labeling adjacent sections with 5HT antisera [40].
• Microdialysis studies in rats have shown a maximal increase in 5-HT concentration in raphe nuclei after systemic infusion of selective serotonergic re-uptake inhibitors (SSRIs) [41].
• We examined in rat: (1) the time-course and magnitude of change in cortical blood flow (CoBF) following electrical stimulation of the dorsal raphe nucleus (DRN) and (2) whether DRN lesions affect resting CoBF or the cerebrovascular response to CO2 [42].
• Immobilization stress elevates tryptophan hydroxylase mRNA and protein in the rat raphe nuclei [43].
• Bilateral adrenalectomy did not prevent the IMO-triggered increase in TPH immunoreactive protein in the raphe nuclei [43].

References