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 rewarding effects of addictive drugs such as opiates and ethanol. We recently showed that opiate peptides reduced both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in NAcc neurons of a slice preparation, with naloxone (Nal) reversal (Yuan et al., 1992). To test other addictive drugs, we used intracellular recording in this rat NAcc slice preparation to investigate ethanol actions on NAcc neuronal properties. Ethanol 22 to 66 mM had little reproducible effect on membrane potential or input slope resistance, but reduced the amplitude of EPSPs 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, respectively. Superfusion of 11 mM ethanol had no effect. To confirm a direct ethanol action on EPSPs, we tested 44 mM ethanol in the presence of 30 microM bicuculline to block IPSPs. In these cells ethanol still decreased EPSP size, suggesting GABAAergic IPSPs are not involved in this effect. 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 resting membrane potentials in the NAcc, we applied the opiate antagonist Nal together with ethanol. Nal 1 to 2 microM significantly reversed ethanol (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.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Yuan
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Madamba
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Siggins
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D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology*; D005971:Glutamates / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000427:Alcohol Deterrents; D005971:Glutamates; D009270:Naloxone; D000431:Ethanol