A role for midbrain raphe gamma aminobutyric acid neurons in 5-hydroxytryptamine feedback control

Abstract

New data show that 5-hydroxytryptamine (5-HT) neurons of the dorsal raphe nucleus (DRN) are subject to feedback control from 5-HT2 receptors, but the circuitry involved is uncertain. This study investigated whether 5-HT2 receptor agonism activates DRN gamma-aminobutyric acid (GABA) neurons, which are known to inhibit neighbouring 5-HT neurons. Systemic administration of the 5-HT2 receptor agonist, DOI, caused a striking increase in Fos-immunoreactivity in the DRN. This effect was abolished by the 5-HT2 antagonists ritanserin and MDL 100907, but not SB 206553, indicating the involvement of 5-HT2A receptors. Importantly, DOI-induced Fos-immunoreactivity in the DRN was extensively colocalized in GAD67-immunoreactive neurons. These findings suggest that activated local GABA neurons may play an important role in 5-HT2 receptor-mediated feedback control of DRN 5-HT neurons.