Diaz, Paula; Baptista, Gabriella; Obray, J Daniel; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences; Psychology)
The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic DA system underlies the rewarding properties of alcohol. The aim of the present study was to help reconcile the relative insensitivity of DA neurons to ethanol in vitro (EC50 = 96 mM) with the sensitivity of DA neurons in vivo (EC50 = 3 mM). To do this we investigated the role of peripheral dopamine 2 receptor (D2R) mediated neuroimmune responses in ethanol enhancement of DA release in the NAc and ethanol reward. We found that systemic administration of ethanol (0.5-4.0 g/kg) markedly enhanced DA release in the NAc while pretreatment with a peripheral-only D2 receptor (D2R) antagonist blocked these effects. A place conditioning paradigm was used to test rats for ethanol preference. Administration of a peripheral D2R antagonist before ethanol conditioning trials was found to prevent acquisition of ethanol conditioned place preference. Finally, ethanol suppression of locomotor activity in rats was attenuated by domperidone pre-administration. Domperidone pre-administration did not affect ethanol impairment of motor coordination. These findings suggest that ethanol enhancement of DA release, intoxication, and ethanol reward are all mediated, at least in part, by a peripheral mechanism involving D2Rs. These results challenge the dogma regarding direct ethanol actions on mesolimbic DA transmission and potentially provides novel pharmacological targets for the treatment of alcohol use disorder.