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

Abstract

We studied the control of dorsal raphe (DR) serotonergic neurons by dopaminergic transmission in rat brain using microdialysis and single unit extracellular 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 (in DR and striatum) and 1 mg/kg s.c. raclopride (in DR). 5-HT1A receptor blockade potentiated the 5-HT increase produced by apomorphine in the DR. Apomorphine (50-400 μg/kg i.v.) increased the firing rate of most 5-HT neurons, an effect prevented by SCH 23390 and raclopride. Quinpirole (40-160 μg/kg 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) D2 receptor transcript was almost absent in the DR and abundant in the substantia nigra (SN) and the periaqueductal grey matter (PAG). Using dual probe microdialysis, the application of tetrodotoxin or apomorphine in SN significantly increased the DR 5-HT output. Thus, the discrepancy between local and systemic effects of dopaminergic agonists and the absence of DA D2 receptor transcript in 5-HT neurons suggest that DA D2 receptors outside the DR control serotonergic activity.