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.