Obesity-resistant S5B rats showed greater cocaine conditioned place preference than the obesity-prone OM rats.

BACKGROUND Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. METHODS OM and S5B/P rats were conditioned with cocaine (5 or 10mg/kg) in one chamber and saline in another for 8days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20mg/kg) on cocaine preference were then assessed in subsequent test sessions. RESULTS OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5mg/kg cocaine and in OM rats treated with 10mg/kg cocaine. CONCLUSION Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.