Involvement of dopamine D₂ receptors in apomorphine-induced facilitation of forebrain serotonin output

The effect of systemic administration of the nonselective dopamine receptor agonist apomorphine on efflux of serotonin (5-hydroxytryptamine, 5-HT) in striatum and hippocampus of freely moving rats was examined using in vivo microdialysis. 5-HT efflux was increased by a moderate dose of apomorphine sufficient for a postsynaptic dopaminergic effect (0.5 mg/kg, s.c.), but not by a lower dose (0.1 mg/kg, s.c.), that acts preferentially on presynaptic dopamine receptors. This effect was blocked by a dopamine D₂ receptor antagonist raclopride, administered either systemically or locally into striatum, but not by a 5-HT(1A) receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide 3HCl (WAY-100635). This indicates that dopamine D₂ receptors, and not 5-HT(1A) receptors, mediate the facilitatory effect of apomorphine, and that this effect occurs at the nerve terminal level. Behavioral effects of apomorphine outlasted the concomitant changes in 5-HT efflux, suggesting that these changes resulted from dopaminergic receptor activation, rather than from the drug-induced behavioral arousal. Copyright (C) 1998 Elsevier Science B.V. All rights reserved.