Plasticity of GABAergic Synapses in the Ventral Tegmental Area During Withdrawal from In Vivo Ethanol Administration

Abstract : Ethanol consummatory behavior seems modulated through GAEAA receptors in the ventral tegmental area (VTA). Previous exposure to ethanol enhances ethanol self-administration, but the mechanisms underlying this phenomenon is poorly understood. The purpose of Specific aim 1 was to examine changes occurring at GABA synapses onto VTA DA neurons after a single in vivo exposure to ethanol, and we have accomplished it. We observed that a single in vivo exposure to ethanol both shifted paired-pulse facilitation (PPF) to paired pulse depression (PPD) and increased ethanol self-administration. An increased frequency of spontaneous miniature GABAA IPSCs (mIPSCs) was also observed in the ethanol-treated animals. Further, the shift to PPD in the ethanol treated mice depended upon activation of presynaptic GABAa receptors. Forskolin increased the amplitude of GABAA IPSCs and the frequency of mIPSCs in the saline- but not in the ethanol-treated mice. Conversely, a protein kinase A (PKA) inhibitor significantly decreased both frequency of spontaneous mIPSCs and amplitude of GABAA IPSCs in the ethanol-treated mice. Our results indicate that potentiation of GABAergic synapses, via a PKA-dependent mechanism, occurs in the VTA after a single in vivo ethanol exposure, and such a potentiation might be a key synaptic modification underlying increased ethanol intake.