Rodent studies26–29 have implicated alterations in the subunit composition of brain AMPARs in diverse aspects of opioid addiction. Increased expression of GluA1-containing/GluA2-lacking AMPARs has been observed in the central nucleus of the amygdala26 and the hippocampal PSD28 in studies of morphine-related context-reward conditioning26 and context-dependent behavioral sensitization.28 The latter 28 found that these changes were mediated via interactions with TARP gamma-8 and GRIP1 proteins. GluA1 knockout mice displayed impaired drug-induced state dependency after operant conditioning with morphine.29 Another study27 implicated down-regulation of GluA2 expression in the prefrontal cortex in reinstatement of heroin self-administration after prolonged abstinence. Interestingly, CNIH3 expression is greatest in the frontal cortex, amygdala, and hippocampus in the adult human brain.58
