ETHANOL DECREASES GLUTAMATERGIC SYNAPTIC TRANSMISSION IN RAT NUCLEUS-ACCUMBENS IN-VITRO - NALOXONE REVERSAL

The nucleus accumbens septi (NAcc) is a key brain region in the reward ing effects of addictive drugs such as opiates and ethanol. We recentl y showed that opiate peptides reduced both excitatory and inhibitory p ostsynaptic potentials (EPSPs and IPSPs) in NAcc neurons of a slice pr eparation, with naloxone (Nal) reversal (Yuan et a/., 1992). To test o ther addictive drugs, we used intracellular recording in this rat NAcc slice preparation to investigate ethanol actions on NAcc neuronal pro perties. Ethanol 22 to 66 mM had little reproducible effect on membran e potential or input slope resistance, but reduced the amplitude of EP SPs evoked by stimulation of the peri-tubercle region ventral to NAcc. Ethanol 22, 44 and 66 mM all significantly decreased the EPSPs evoked by half-maximal stimulation to 80, 60 and 68% of control, respectivel y. Superfusion of 11 mM ethanol had no effect. To confirm a direct eth anol action on EPSPs, we tested 44 mM ethanol in the presence of 30 mu M bicuculline to block IPSPs. In these cells ethanol still decreased E PSP size, suggesting GABA(A)ergic IPSPs are not involved in this effec t. The glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione abolished the EPSPs evoked at resting membrane potentials. As ethanol actions mimic those of opiates in reducing EPSPs without effect on re sting membrane potentials in the NAcc, we applied the opiate antagonis t Nal together with ethanol. Nal 1 to 2 muM significantly reversed eth anol (44 mM) reduction of EPSP amplitude. Thus, our data suggest that a major effect of intoxicating concentrations of ethanol in NAcc is to reduce glutamatergic synaptic transmission. The results show a striki ng similarity between mechanisms of ethanol and opiate effects in NAcc , and suggest that ethanol may act via some opiate mechanism.