Alterations in expression and phosphorylation of GluA1 receptors following cocaine-cue extinction learning

Brain regional analyses of total GluA1 and GluA1-pSer845 were used to delineate plasticity of the AMPA receptor in conjunction with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a 2-s light cue and later underwent a single 2 h extinction session for which cocaine was withheld but response-contingent cues were presented. Control groups received yoked-saline sessions or received cocaine self-administration training without undergoing extinction training. Extinction-related increases and decreases, respectively, in total GluA1 were observed in the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA). Phosphorylation of GluA1 at Ser845 was increased in the vmPFC and nucleus accumbens (NAc). Though total GluA1 did not change in NAc, there was a positive association between the number of responses during extinction training and the magnitude of total GluA1 in NAc. No significant changes were evident in the dorsal hippocampus. We conclude that the BLA and vmPFC, in particular, appear to be loci for the inhibition of learned behavior induced via extinction training, but each site may have different signaling functions for cocaine-cue extinction learning.

► Cocaine-cue extinction increased and decreased, respectively, total GluA1 in vmPFC and BLA. ► Cocaine-cue extinction increased GluA1-pSer845 in vmPFC and NAc. ► Lever responding positively correlated with total GluA1 in NAc. ► The BLA and vmPFC appear to be loci for cocaine-cue extinction learning. ► Understanding extinction mechanisms may improve exposure therapy in cocaine addicts.