The heightened risk of cue-induced cocaine seeking (incubation of craving) that occurs during prolonged withdrawal (protracted abstinence in humans) has provided new insights into the molecular basis of vulnerability to relapse. During incubation in animal models, AMPA-type glutamate receptors are recruited. Specifically, the infralimbic medial prefrontal cortex-to-nucleus accumbens shell circuit recruits calcium-permeable AMPA receptors,144 and the prelimbic medial prefrontal cortex-to-nucleus accumbens core circuit recruits non-calcium-permeable AMPA receptors. The blockade of metabotropic glutamate 1 receptors in the nucleus accumbens blocks cue-induced incubation reinstatement and cocaine-primed reinstatement; as a result, these receptors are potential therapeutic targets.145,146
