Melis et al. (2002) linked the long-lasting potentiation of GABAergic synapses on dopaminergic neurons in the VTA by systemic EtOH to an effect on presynaptic GABAB receptors. Moreover, the frequency (but not the amplitude) of mIPSCs was also significantly higher in VTA neurons of EtOH-treated animals compared to controls, further supporting an increased probability of presynaptic GABA release independent of neuronal discharge in VTA neurons treated with EtOH. Interestingly, the GABAB receptor antagonist, CGP 35348, shifted PPD to PPF in EtOH-treated animals by increasing the amplitude of the second evoked GABAA IPSC and without affecting GABAA IPSC in the saline-treated animals. In addition, both the frequency and the amplitude of mIPSCs were unaffected by CGP 35348 in both groups of mice. Thus, the PPD observed in the EtOH-treated mice could result from an increased probability of GABA release, which might in turn lead to activation of presynaptic GABAB receptors and decrease the second IPSC. These results further support the hypothesis that GABA levels are increased after EtOH exposure, leading to spillover onto presynaptic GABAB receptors, whose activation leads to inhibition of release (Hausser and Yung 1994; Melis et al. 2002).
