Chronic drug exposure leads to adaptive changes of inhibitory transmission onto VTA DA neurons (Liu et al., 2005). After several daily injections of cocaine baseline inhibitory transmission becomes depressed. The induction requirements of this plasticity remain largely unknown, but appear to involve priming by BDNF (Pu et al., 2006). Its expression relies on a redistribution of GABA-ARs in the postsynaptic membrane. The major consequence of this downregulation of GABAergic transmission has been proposed to be a lower threshold for the induction of subsequent spike-timing dependent LTP at glutamatergic synapses (Liu et al., 2005). However, other groups have found that this form of LTP is reduced following cocaine administration (Luu and Malenka, 2008; Argilli et al., 2008). Once again, to understand the circuit repercussions of these drug-evoked synaptic adaptations it will be crucial to determine which specific projections are modified, the one directly arising from the NAc, the RMTg or local inputs from interneurons.
