The behavioral relevance of drug-evoked synaptic plasticity in the NAc has been examined in several studies. To test whether LTD in the NAc was required for amphetamine-induced behavioral sensitization, a membrane permeable peptide that prevents endocytosis of AMPARs and thus NMDAR-dependent LTD was infused into the NAc of sensitized rats immediately prior to a challenge dose of amphetamine (Brebner et al., 2005). This manipulation prevented the increase in locomotor activity normally elicited by amphetamine suggesting that drug-elicited LTD in the NAc is required for the expression of behavioral sensitization. More recently, the behavioral importance of the impairment of NMDAR-dependent LTD in the NAc caused by cocaine has been addressed by taking advantage of the observation that following prolonged cocaine self-administration, only a modest proportion of rats develop behaviors analogous to human addicts (Deroche-Gamonet et al., 2004; Kasanetz et al., 2010). Although approximately two weeks following the cessation of cocaine self-administration, LTD was impaired in all animals, the ability to generate LTD slowly recovered in “non-addicted” animals. In contrast, “addicted” animals expressed persistently impaired LTD (Kasanetz et al., 2010). If LTD
