Dopamine has been implicated as one of the primary neurotransmitters responsible for mediating the reinforcing properties of various substances of abuse, including ethanol. We have investigated the effect of local perfusion of ethanol into certain brain areas on extracellular dopamine, and its metabolites DOPAC (di-hydroxyphenylacetic acid) and HVA (homovanillic acid). We have demonstrated that ethanol increases extracellular dopamine concentrations in a dose-related fashion. This increase in dopamine was dependent on normal calcium channel function and occurred at brain concentrations relevant to intoxication in humans (<100mM). We have also shown that the different alcohols exhibit a structure-activity relationship with regard to their ability to increase dopamine with butanol> ethanol> methanol. Pretreatment with antagonists at 5-HT3 receptors effectively attenuated the ethanol-induced increase in dopamine levels. Current research is focussed on further elucidating the nature of this dopamine increase. In addition, we are developing studies to investigate the effects of ethanol on dopamine function in chronically ethanol treated animals.
