Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving

These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.

We used shRNA targeted to the RA degradative enzyme Cyp26b1 to increase RA signaling. This treatment accelerated incubation; rats expressed incubation on abstinence day (AD) 15, when it is not yet detected in control rats. It also accelerated CP-AMPAR synaptic insertion measured with slice physiology. CP-AMPARs were detected in Cyp26b1 shRNA-expressing MSN, but not control MSN, on AD15-18. Next, we used shRNA targeted to the major RA synthetic enzyme Aldh1a1 to reduce RA signaling. In MSN expressing Aldh1a1 shRNA, synaptic CP-AMPARs were reduced in late withdrawal (AD42-60) compared to controls. However, we did not detect an effect of this manipulation on incubated cocaine seeking (AD40). Conclusions: These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.