Effects of cannabinoid drugs on the reinforcing properties of food in gestationally undernourished rats.

Involvement of the endocannabinoids in hyperphagia has been demonstrated, however, behavioral characterization of its role in food reinforcement is limited. The present study investigated whether 2-arachidonoyl glycerol, an endocannabinoid ligand, and rimonabant, a CB1 antagonist, change the reinforcing properties of food in gestationally undernourished rats (a putative model of obesity) vs controls. Albino dams were food deprived by 0 to 45% of their free-feeding weights up to day 18 of their gestational period. Their offspring were allowed to free-feed until postnatal day 75. Then, behavior of the offspring was placed under progressive ratio schedules of sucrose reinforcement. After baseline data were established, intraperitoneal injections of 2-AG (0.03-3.75 mg/kg), and rimonabant (SR141716, 0.3-3.0 mg/kg) were administered and compared across group. Results show gestationally undernourished (GU) rats as adults weighed less than controls at the time of testing and female offspring allowed to free-feed for over 35 weeks exhibited lower body weights than controls. Under baseline, GU rats had lower breakpoints than controls. 2-AG and rimonabant significantly increased and decreased, respectively, breakpoint and responses made per session, suggesting involvement of the cannabinoid system in food reinforcement. When comparing peak doses of 2-AG on breakpoint, gestationally undernourished rats exhibited lower peak doses than controls. These data suggest that under the gestation deprivation method employed, GU rats were thinner and had lower food reinforcer efficacy than controls, and may have heightened sensitivity to 2-AG.