Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The release of 5-HT in terminal areas of the rodent brain is regulated by 5-HT1B receptors. Here we examined the role of 5-HT1B receptors in the control of 5-HT output and firing in the dorsal raphe nucleus (DR), median raphe nucleus (MnR) and forebrain of the rat in vivo. The local perfusion (30-300 microM) of the selective 5-HT1B receptor agonist CP-93,129 to freely moving rats decreased 5-HT release in the DR and more markedly in the MnR. Likewise, 300 microM CP-93,129 reduced 5-HT output in substantia nigra pars reticulata, ventral pallidum, lateral habenula and the suprachiasmatic nucleus. The effect of CP-93,129 was prevented by SB-224289, but not by WAY-100635, selective 5-HT1B and 5-HT1A receptor antagonists, respectively. SB-224289 did not alter dialysate 5-HT in any raphe nuclei. The intravenous administration of the brain-penetrant selective 5-HT1B receptor agonist CP-94,253 (0.5-2.0 mg/kg) to anesthetized rats decreased dialysate 5-HT in dorsal hippocampus and globus pallidus, increased it in MnR and left it unaltered in the DR and medial prefrontal cortex. SB-224289, at a dose known to block 5-HT1B autoreceptor-mediated effects (5 mg/kg), did not prevent the effect of CP-94,253 on MnR 5-HT. The intravenous administration of CP-94,253 (0.05-1.6 mg/kg) to anesthetized rats increased the firing rate of MnR, but not DR-5-HT neurons. The local perfusion of CP-94,253 in the MnR showed a biphasic effect, with 5-HT reductions at 0.3-3 microM and increase at 300 microM. These results suggest that 5-HT cell firing and release in midbrain raphe nuclei (particularly in the MnR) are under control of 5-HT1B receptors. The activation of 5-HT1B autoreceptors (possibly located on 5-HT nerve endings and/or varicosities within DR and MnR) reduces 5-HT release. The effects of higher concentrations of 5-HT1B receptor agonists seem more compatible with the activation of 5-HT1B heteroreceptors on inhibitory neurons.
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PMID:The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. 1159 69

Basic and clinical studies suggest that neurokinin 1 (NK1) receptor antagonists have efficacy in the treatment of affective disorders through effects on the dorsal raphe nucleus (DR), a source of forebrain-projecting serotonin (5-HT) neurons that has also been implicated in affective disorders. To investigate the regulation of the DR-5-HT system by NK1 receptors, the effects of substance P (an NK1 agonist) on rat DR neuronal activity were characterized. Most of the DR neurons (83%; n = 47 total) were inhibited by substance P microinfusion into the DR, and in some cases (17%) this was preceded by a brief activation. Pure excitation was observed in a small population of neurons (17%) that were localized in the dorsal DR, where NK1 receptors are most dense. Sendide, a selective NK1 antagonist, attenuated the effects of substance P, indicating that they were mediated by NK1 receptor activation. The selective 5-HT1A antagonist, WAY 100635, administered systemically or into the DR, prevented the inhibitory effects of substance P, implicating DR 5-HT1A receptors in this response. Finally, microinfusion of the excitatory amino acid antagonist, kynurenic acid, into the DR prevented both excitatory and inhibitory effects. The results suggest that NK1 receptor activation in the DR excites a population of 5-HT neurons via glutamatergic transmission. This results in 5-HT release throughout the DR, activation of 5-HT1A receptors, and subsequent inhibition. Interactions between NK1 and 5-HT1A receptors within DR neural networks may contribute to the mechanism of action of novel antidepressants acting at NK1 receptors.
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PMID:Substance P Acts through local circuits within the rat dorsal raphe nucleus to alter serotonergic neuronal activity. 1290 75