A limited and intermittent access to a high-fat diet modulates the effects of cocaine-induced reinstatement in the conditioned place preference in male and female mice.

Rationale: Palatable food and drugs of abuse activate common neurobiological pathways and numerous studies suggest that fat consumption increases vulnerability to drug abuse. In addition, preclinical reports show that palatable food may relieve craving for drugs, showing that an ad libitum access to a high-fat diet (HFD) can reduce cocaine-induced reinstatement.

Objective: The main aim of the present study was to evaluate the effect of a limited and intermittent exposure to HFD administered during the extinction and reinstatement processes of a cocaine-induced conditioned place preference (CPP).

Methods: Male and female mice underwent the 10 mg/kg cocaine CPP. From post-conditioning onwards, animals were divided into four groups: SD (standard diet); HFD-MWF with 2-h access to the HFD on Mondays, Wednesdays, and Fridays; HFD-24h, with 1-h access every day; and HFD-Ext with 1-h access to the HFD before each extinction session.

Results: Our results showed that all HFD administrations blocked reinstatement in males, while only the HFD-MWF was able to inhibit reinstatement in females. In addition, HFD-Ext males needed fewer sessions to extinguish the preference, which suggests that administration of fat before being exposed to the environmental cues is effective to extinguish drug-related memories. HFD did not affect Oprμ gene expression but increased CB1r gene expression in the striatum in HFD-Ext males.

Conclusions: These results support that palatable food could act as an alternative reward to cocaine, accelerating extinction and blocking reinstatement, these effects being sex specific.