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.
Olausson
P
P
Department of Pharmacology, Göteborg University, Sweden.
Ericson
M
M
Petersson
A
A
Kosowski
A
A
Söderpalm
B
B
Engel
J A
JA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D000431:Ethanol; D006719:Homovanillic Acid; D010879:Piperazines; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C051752:nefazodone