Expression of many of the genes responsible for GABA synthesis, transport into synaptic vesicles, and retrieval from the synaptic cleft rose following cocaine treatment and increased further during withdrawal. Daily cocaine injections decreased GABAA receptor-mediated maximal evoked currents and miniature inhibitory postsynaptic currents on dopamine neurons in the VTA (Liu et al., 2005); furthermore, GABAA receptor function has been implicated in dopamine-mediated alcohol reward (Heilig et al., 2011). GABAB receptor agonists attenuated cocaine reinforcement and reduced cocaine craving in a study of human cocaine users (Brebner et al., 2002); while the precise mechanism of these behavioral effects is unknown, activation of GABAB receptors in the NAc reduces dopamine release from dopaminergic projections from the VTA (Erhardt et al., 2002). Changes in GABAA receptor subunit expression, which fell during withdrawal, and in GABAB receptor expression, which rose, could contribute significantly to altered synaptic transmission.
