Dietary conditions and highly palatable food access alter rat cannabinoid receptor expression and binding density

Abstract

Endogenous cannabinoid signaling, mediated predominately by CB1 receptor activation, is involved in food intake control and body weight regulation. Despite advances in determining the role of the CB1 receptor in obesity, its involvement in the driven nature of eating pathologies has received little attention. The present study examined CB1 receptor alterations as a consequence of dietary-induced binge eating in female Sprague Dawley rats. Four control groups were used to control for calorie restriction and highly palatable food variables characterizing this behavioral model. All groups were kept on their respective feeding schedules for 6-weeks and were given a uniform 33% calorie restriction (~22 h food deprivation) prior to sacrifice. Our findings indicate that regional CB1 mRNA and density were influenced by dietary conditions, but were not specific to the dietary-induced binge eating paradigm used. An increase of approximately 50% (compared with naive controls) in CB1 receptor mRNA levels in the nucleus of the solitary tract as measured by in situ hybridization was found in animals receiving continuous access to a highly palatable food (i.e., vegetable shortening with 10% sucrose). This group also had a significant increase in body weight and adiposity. An approximate 20% reduction in CB1 mRNA was observed in the cingulate cortex (areas 1 and 2) in animals exposed to an intermittent schedule of feeding, compared with groups that had ad libitum feeding schedules (i.e., continuous access and naive controls). Receptor density as measured by [(3)H]CP55,940 autoradiography, was reduced by approximately 30% in the nucleus accumbens shell region in groups receiving repeated access to the highly palatable food. Taken together, these findings indicate that dietary conditions can differentially influence CB1 receptors in forebrain and hindbrain regions.

Figure 1. In situ hybridization of CB1 receptors in the nucleus of the solitary tract (NTS) following the feeding schedules

A: Representative pseudocolor images from in situ hybridization for CB1 receptor. B: Group differences were found in the NTS (P<0.05). The Continuous Access group differed from Binge Access and Naive (*, p<0.05 for both). Dotted line represents value for the Naive group for comparison. There were no differences between groups when body weight was used as a covariate in an ANCOVA, suggesting that body weight differences influenced CB1 receptor group differences.

Figure 2. In situ hybridization of CB1 receptors in the cingulate cortex (Cg1 and Cg2) following the feeding schedules

A: Representative pseudocolor images from in situ hybridization for CB1 receptor. B: Group differences were found in the cingulate cortex (P<0.005). The Continuous Access group differed from Binge Access, Chow Restricted, and Scheduled Access groups (*, p<0.05 for all). Dotted line represents value for the Naive group for comparison. Planned comparisons revealed there was a significant decrease in the CB1 receptor mRNA in groups that received intermittent schedules compared with those with ad libitum schedules, regardless of food palatability.

Figure 3. Autoradiography of CB 1 receptor in the nucleus accumbens medial shell region

A: Representative images from [H3] CP55940 for CB receptor densities. B: Group differences were found in the nucleus accumbens (P<0.05). Post-hoc testing revealed the Binge Access, Continuous, Scheduled Access groups demonstrated decreased receptor densities relative to the Chow Restricted group (*, p<0.05, for all).Dotted line represents value for the Naive group for comparison.