Abstract

Past research has demonstrated that the motivational effects of opiates causes a change in ventral tegmental area (VTA) γ-amino butyric acid (GABA) subtype A receptor [GABA(A)R] complexes in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of VTA GABA neurons to a GABA-induced depolarization. Previously shown in naïve animals, superfusion of ethanol (IC50 = 30 mM) and the GABA(A)R agonist muscimol (IC50 = 100 nM) decreased VTA GABA neuron firing rate in a dose-dependent manner. The aim of this study was to evaluate VTA GABA neuron excitability, GABA synaptic transmission to VTA GABA neurons, and a potential switch in GABA(A)R functionality produced by alcohol dependence. To accomplish these studies, we used standard whole-cell, perforated patch, and attached-cell mode electrophysiological techniques to evaluate chronic ethanol effects on VTA GABA neurons in CD-1 GAD GFP mice, which enable the visual identification of GABA neurons in the slice preparation. In order to more conclusively demonstrate synaptic plasticity in VTA neurons associated with alcohol dependence, three studies were proposed to elucidate the mechanism underlying the switch in GABA synaptic function with dependence. First, we evaluated the effects of withdrawal from chronic ethanol exposure on muscimol-induced inhibition of VTA GABA neuron firing rate. Second, we evaluated the effects of withdrawal from chronic ethanol exposure on GABA(A)R-mediated synaptic responses in VTA GABA neurons by looking at eIPSCs, and corresponding changes in VTA DA neuron firing rate. Third, we evaluated chloride reversal potentials in VTA GABA neurons using perforated patch recordings in VTA GABA neurons.Through these studies, we found that there was less sensitivity to muscimol in animals treated with ethanol versus air-exposed controls. However, it is yet to be shown more conclusively if VTA GABA neurons undergo a switch in GABA(A)R function with chronic ethanol.

Degree

College and Department

Life Sciences; Physiology and Developmental Biology

Rights

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