Effects of withdrawal from intermittent vs. long access cocaine self-administration on nucleus accumbens calcium permeable AMPA receptor transmission and incubation of craving in female and male rats

RATIONALE: Following the discontinuation of long access (LgA) to cocaine self-administration rats show a time-dependent increase in motivation for drug ("incubation of craving") thought to be mediated by enhancements in transmission via nucleus accumbens (NAc) calcium-permeable AMPA receptors (CP-AMPARs). Intermittent access (IntA) to cocaine produces even more robust addiction-like behavior than LgA, but it is not known if this produces comparable incubation of craving and effects on CP-AMPARs. METHODS: Rats underwent 5 days of short access training followed by 10 days of LgA or IntA cocaine self-administration; drug naïve rats served as controls. Some rats were used for within-subject incubation testing at withdrawal days 1, 30 and 45, while others were used to measure the effects of LgA and IntA experience on CP-AMPAR-mediated transmission at withdrawal day 30-35. RESULTS: IntA and LgA self-administration followed by withdrawal resulted in similar patterns of incubation across both sexes. Additionally, CP-AMPAR-mediated transmission was similarly enhanced in LgA and IntA groups compared to drug naïve animals. CONCLUSIONS: Despite much less total cocaine consumption IntA resulted in incubation of craving and enhancements in NAc CP-AMPAR plasticity similar to LgA. This adds to a growing literature demonstrating that the intermittency of cocaine consumption can produce robust neurobehavioral plasticity comparable to LgA, in the absence of high levels of cocaine consumption.