Adaptive responses of gamma-aminobutyric acid neurons in the ventral tegmental area to chronic ethanol

We have recently identified a homogeneous population of gamma-aminobutyric acid (GABA)-containing neurons in the ventral tegmental area (VTA), an area implicated in the reinforcing properties of alcohol. We evaluated the effe cts of local and systemic ethanol on VTA GABA neuron spontaneous activity i n ethanol naive and chronically treated freely behaving rats and in anesthe tized rats. In freely behaving animals, acute i.p. administration of 0.2 to 2.0 g/kg ethanol reduced the firing rate of VTA GABA neurons. Chronic admi nistration of 2.0 g/kg i.p. ethanol enhanced baseline activity of VTA GABA neurons and induced tolerance to ethanol inhibition of their firing rate. I n a separate group of freely behaving animals, tolerance to 0.4 to 2.0 g/kg i.p. ethanol-induced inhibition of VTA GABA neuron firing rate was observe d following 2 weeks of chronic exposure to ethanol vapors producing intermi ttent blood alcohol levels of 158 mg/100 ml. In acute studies in halothane- anesthetized animals, ethanol applied locally into the VTA decreased the sp ontaneous firing rate of VTA GABA neurons, whereas systemic ethanol produce d an early inhibition followed by a late excitation at 30 to 60 min after t he ethanol injection, suggesting that ethanol modulation of an extrinsic in put may excite VTA GABA neurons. Tolerance to local ethanol inhibition of V TA GABA neuron firing rate was produced by 2 weeks of chronic exposure to i ntermittent ethanol vapors. These results demonstrate the marked sensitivit y of these neurons to ethanol and suggest that chronic ethanol administrati on produces selective adaptive circuit responses within the VTA or in extra tegmental structures that regulate VTA GABA neuron activity.