An opposing role for prelimbic cortical projections to the nucleus accumbens core in incubation of craving for cocaine versus water

Background: Both drug and natural reward-seeking have been shown to increase following an extended period of abstinence, a phenomenon termed 'incubation of craving'. Although this phenomenon involves many brain regions, the projections from the prelimbic cortex (PrL) to the nucleus accumbens (NAc) core have been strongly implicated in incubation of cocaine-seeking. However, this circuit has not been investigated in the context of incubation of craving for natural rewards.

Methods: Male Long Evans rats were trained to self-administer cocaine or water/saline 6 h/d for 14 days and subsequently entered 1 month of experimenter-imposed abstinence. Rats then underwent an optogenetic stimulation protocol used to induce long term depression in the PrL terminals to the NAc core immediately before beginning an extinction test used to assess incubation of craving.

Results: Control cocaine rats showed heightened drug-seeking on day 30 when compared to day 1 of abstinence, demonstrating incubation of craving. Notably, optogenetic stimulation of the PrL to NAc core pathway blocked this behavior in cocaine rats. In contrast, optogenetic stimulation of the PrL to NAc core pathway induced incubation of craving in water/saline rats.

Conclusions: These findings suggest that neuroadaptations in the PrL to NAc core pathway play opposing roles in the incubation of craving for cocaine versus water.