Effects of rimonabant on behavior maintained by progressive ratio schedules of sucrose reinforcement in obese Zucker (fa/fa) rats

Abstract

This experiment reports on the ability of rimonabant to alter the reinforcing properties of food in the genetically obese Zucker (fa/fa) rat, a strain that exhibits higher levels of endocannabinoids in brain regions that correspond to heightened food intake. We characterized food reinforcement in obese and lean Zucker rats by placing behavior under progressive ratio schedules of sucrose reinforcement. Then, doses of rimonabant (1-10 mg/kg), a CB1 receptor antagonist, were administered. Obese Zuckers had slightly higher breakpoints for sucrose under baseline conditions compared with leans, and also demonstrated significantly higher response rates than leans. Rimonabant dose-dependently decreased breakpoints and response rates for both groups, though only obese Zuckers demonstrated suppressed behavior under the 1 mg/kg dose. The 10 mg/kg dose of rimonabant reduced breakpoints equally for both groups (by about 60%). This dose of rimonabant also reduced food intake by 20% in lean Zuckers, and by 30% in obese Zuckers. These findings extend the literature that rimonabant reduces food reinforcer efficacy, and suggest that obese Zuckers may exhibit a heightened sensitivity to rimonabant. The findings also suggest that the effort required to obtain food reinforcement may also play a role in the efficacy of rimonabant.

Effects of 2-AG on the reinforcing properties of wheel activity in obese and lean Zucker rats

“…This difference supports the hypothesis that obese rats exhibit a greater sensitivity to 2-AG than lean rats. This finding also supports other research showing that obese Zuckers are more sensitive to cannabinoid drugs, such as the antagonist rimonabant (Rasmussen and Huskinson, 2008). Sensitivity to 2-AG and rimonabant may be linked to obese Zuckers having higher basal levels of 2-AG in their brains (DiMarzo et al, 2001) and higher densities of CB1 receptors in limbic areas of the brain (Thanos et al, 2008).…”

“…First, the data extend the literature on wheel running as a reinforcer in standard laboratory rodent strains (Skinner, 1932;Kagan and Berkun, 1953;Collier and Hirsch, 1971;Jennings and McCutcheon, 1974;Stewart et al, 1985;Eikelboom and Mills, 1988;Belke, 1997;Sherwin, 1998) to the genetically obese Zucker rat strain. Second, the results also extend the literature on PR schedules by showing that the reinforcing efficacy of wheel running, like food, water, and drugs (Glass et al, 1999;Solinas et al, 2003;Solinas and Goldberg, 2005;Madden et al, 2007;Rasmussen and Huskinson, 2008;Wakley and Rasmussen, 2009) can be characterized using PR schedules.…”

“…In this study, we did not prefeed our rats before the operant sessions. Moreover, they were equally food deprived, as we used a 2-h free-feed session that took place 21 h before the experimental session, which resulted in rats in both groups consuming about 2.3% of their body weights during the free-feed sessions (Rasmussen and Huskinson, 2008). Thus, the differences in behavior in this study seem to be due solely to body weights, rather than not deprivation.…”

“…Interestingly, the results of this study identified behavioral suppression effects of 2-AG, which have not been reported earlier. It may be the case that excessive ECB activity in the context of obesity may not only increase overeating by making food more reinforcing (Solinas and Goldberg, 2005;Rasmussen and Huskinson, 2008;Wakley and Rasmussen, 2009), but may also decrease activity by suppressing the reinforcing properties of exercise. Future studies may further examine this relationship.…”

“…DiMarzo et al, 2001;Kirkham et al, 2002;Friede et al, 2005;Kirkham, 2005;Solinas and Goldberg, 2005;Keeney et al, 2008;Rasmussen and Huskinson, 2008;Wakley and Rasmussen, 2009). Inactivity, also linked to obesity (e.g.…”