Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat

Background: Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. At most central synapses, ethanol generally increases inhibitory synaptic transmission; however, no studies have explored the effect of acute ethanol on GABAergic transmission in the VTA. Methods: Whole-cell patch clamp recordings of inhibitory postsynaptic currents (IPSCs) from VTA-DA neurons in midbrain slices from young rats. Results Acute exposure of VTA-DA neurons to ethanol (25 to 50 mM) robustly enhanced GABAergic spontaneous and miniature IPSC frequency while inducing a slight enhancement of spontaneous IPSC (sIPSC) amplitude. Ethanol (50 mM) enhanced paired-pulse depression of evoked IPSCs, further suggesting enhanced GABA release onto VTA-DA neurons. The frequency of sIPSCs was suppressed by the GABA(B) agonist, baclofen (1.25 mu M) and enhanced by the antagonist, SCH50911 (20 mu M); however, neither appeared to modulate or occlude the effects of ethanol on sIPSC frequency. Conclusions: The present results indicate that ethanol increases postsynaptic GABA(A) receptor sensitivity, enhances action potential-independent GABA release onto VTA-DA neurons, and that this latter effect is independent of GABA(B) auto-receptor inhibition of GABA release.