Abstract

The serotonin (5-HT)_2A/2C receptor antagonist ritanserin has been reported to potentiate the dopamine (DA) D_2/3receptor antagonist raclopride-induced DA release in medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) but not striatum (STR). Because of reciprocal interactions between 5-HT_2A and 5-HT_1A receptors, we tested the hypothesis that 5-HT_1A receptor agonism also potentiates D_2/3 receptor antagonist-induced DA release using a combination of the 5-HT_1A receptor agonistR(+)-8-hydroxy-2-(di-n-propylamino)-tetralin [R(+)-8-OH-DPAT] and the D_2/3 receptor antagonist S(−)-sulpiride (SUL).R(+)-8-OH-DPAT (0.05 mg/kg s.c.) potentiated low but not high dose SUL (1, 3 but not 10 or 25 mg/kg s.c.)-induced DA release in NAC, but had no effect in STR at all doses tested (1, 3, 10, and 25 mg/kg s.c.). However, R(+)-8-OH-DPAT (0.05 mg/kg s.c.) alone had no effect on basal, potentiated SUL (10 and 25 mg/kg s.c.)-induced DA release in mPFC; the effect of low dose SUL (1 and 3 mg/kg s.c.) was not tested because it alone had no effect on DA release. This potentiation was abolished by pretreatment with the 5-HT_1A receptor antagonist WAY100635 (0.05 mg/kg s.c.), which alone had no effect on DA release. These results suggest that 5-HT_1A receptor agonism facilitates DA release in mPFC and NAC but not STR in combination with D₂ receptor antagonism.