Nefazodone attenuates the behavioral and neurochemical effects of ethanol

This study evaluated the influence of nefazodone, a combined 5-HT2A receptor antagonist and 5-HT reuptake inhibitor, on the behavioral and neurochemical effects of ethanol in nonselected male Wistar rats. In microdialysis experiments, ethanol (2.5 g/kg, i.p.) increased extracellular accumbal dopamine levels by 36% (p = 0.0073) compared to baseline levels, and elevated the maximal DOPAC and HVA levels by 26% (p = 0.0093) and 52% (p = 0.0010), respectively, Nefazodone (50 mg/kg, s.c.) per se increased accumbal dopamine levels by 28% (p = 0.0199) but, when injected 40 min before ethanol, reduced the ethanol-induced elevation of accumbal dopamine overflow (p = 0.0132) and decreased the ethanol-induced HVA levels (p = 0.0159). In an ethanol(6% v/v)/water free-choice paradigm, nefazodone (50 mg/kg, s.c.) decreased ethanol intake by 51% (p = 0.0251) and preference by 22% (p = 0.0251) in high- but not low-preferring rats from a nonselected Wistar strain. These results show that nefazodone modulates the mesolimbic dopamine system in a dopamine activity-dependent manner, and influences the neurochemical and behavioral effects of ethanol in the rat.