Basic and clinical studies suggest that neurokinin 1 (NK1) receptor antagonists have efficacy in the treatment of @entity1316 through effects on the dorsal raphe nucleus (DR), a source of forebrain-projecting @entity750 ( @entity750 ) neurons that has also been implicated in @entity1316 . To investigate the regulation of the DR- @entity750 system by NK1 receptors, the effects of substance P (an NK1 agonist) on @entity35 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 @entity16325 activation. The selective @entity10463 antagonist, @entity10098 , administered systemically or into the DR, prevented the inhibitory effects of substance P, implicating DR @entity10463 receptors in this response. Finally, microinfusion of the excitatory @entity535 antagonist, @entity5373 , into the DR prevented both excitatory and inhibitory effects. The results suggest that @entity16325 activation in the DR excites a population of @entity750 neurons via glutamatergic transmission. This results in @entity750 release throughout the DR, activation of @entity10463 receptors, and subsequent inhibition. Interactions between NK1 and @entity10463 receptors within DR neural networks may contribute to the mechanism of action of novel antidepressants acting at NK1 receptors.

Substance P Acts through local circuits within the XXXX dorsal raphe nucleus to alter serotonergic neuronal activity.

@entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity16325 :: ('24807(Tax:10116)', 'Gene') :: ['NK1 receptor'] @entity10463 :: ('24473(Tax:10116)', 'Gene') :: ['5-HT1A'] @entity1316 :: ('MESH:D019964', 'Disease') :: ['affective disorders'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['serotonin', '5-HT'] @entity10098 :: ('MESH:C090413', 'Chemical') :: ['WAY 100635'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity5373 :: ('MESH:D007736', 'Chemical') :: ['kynurenic acid']
@entity35 :: (10116,Species) :: ['rat']
