Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Sep 2002
Neurokinins activate local glutamatergic inputs to serotonergic neurons of the dorsal raphe nucleus.
It has been proposed that antidepressant effects of neurokinin NK(1) receptor blockade may result from an increase in serotonin (5-HT) transmission. However, the mechanism by which neurokinins influence 5-HT neurons is not known. In this study, local NK(1) and NK(3) receptor-mediated responses in 5-HT neurons of the dorsal raphe nucleus (DRN) were studied using intracellular recording in rat brain slices. ⋯ The SP- and NKB-induced EPSCs were preferentially blocked by NK(1) and NK(3) antagonists, and there was minimal cross-desensitization between agonists at the two receptors. We conclude that neurokinins, via distinct NK(1) and NK(3) receptors, could promote 5-HT transmission, at least in part, by exciting a local population of glutamatergic inputs to 5-HT neurons in the DRN. However, these local excitatory effects, viewed within the context of the global effects of neurokinins on 5-HT neurons, reveal important differences between the functional role of NK(1) and NK(3) receptors.