Control of serotonergic neurons in rat brain by dopaminergic receptors outside the dorsal raphe nucleus

We studied the control of dorsal raphe (DR) serotonergic neurons by dopamin ergic transmission in rat brain using microdialysis and single unit extrace llular recordings. Apomorphine (0.5-3.0 mg/kg s.c.) and quinpirole (0.5 mg/ kg s.c.) increased serotonin (5-HT) output in the DR and (only apomorphine) in striatum. These effects were antagonized by 0.3 mg/kg s.c. SCH 23390 (i n DR and striatum) and 1 mg/kg s.c. raclopride (in DR). 5-HT1A receptor blo ckade potentiated the 5-HT increase produced by apomorphine in the DR. Apom orphine (50-400 mug/kg i.v.) increased the firing rate of most 5-HT neurons , an effect prevented by SCH 23390 and raclopride. Quinpirole (40-160 mug/k g i.v.) also enhanced the firing rate of 5-HT neurons. When applied in the DR, neither drug increased the 5-HT output in the DR or striatum. Likewise, micropressure injection of quinpirole (0.2-8 pmol) failed to increase the firing rate of 5-HT neurons, in situ hybridization showed that the dopamine (DA) D-2 receptor transcript was almost absent in the DR and abundant in t he substantia nigra (SN) and the periaqueductal grey matter (PAG). Using du al probe microdialysis, the application of tetrodotoxin or apomorphine in S N significantly increased the DR 5-HT output. Thus, the discrepancy between local and systemic effects of dopaminergic agonists and the absence of DA D, receptor transcript in 5-HT neurons suggest that DA D-2 receptors outsid e the DR control serotonergic activity.