Sex differences in sucrose reinforcement in Long-Evans rats

Background There are sex differences in addiction behaviors. To develop a pre-clinical animal model to investigate this, the present study examined sex differences in sucrose taking and seeking using Long-Evans rats. Methods Five experiments were conducted using separate groups of subjects. The first two examined sucrose or saccharin preference in two-bottle home cage choice tests. Experiment three assessed sucrose intake in a binge model with sucrose available in home cage bottles. Experiments four and five utilized operant-based procedures. In experiment four rats responded for sucrose on fixed and progressive ratio (FR, PR) schedules of reinforcement over a range of concentrations of sucrose. A final component of experiment four was measuring seeking in the absence of sucrose challenged with the dopamine D1 receptor antagonist SCH23390. Experiment five assessed responding for water on FR and PR schedules of reinforcement. Results When accounting for body weight, female rats consumed more sucrose than water; but there was no sex difference in saccharin preference over a range of saccharin concentrations. When accounting for body weight, females consumed more sucrose than males in the binge model, and only females increased binge intake over 14 days of the study. Females responded at higher rates for sucrose under both FR and PR schedules of reinforcement. Females responded at higher rates in extinction (seeking); SCH23390 reduced sucrose seeking of both females and males. Females responded at higher rates for water on FR and PR schedules than males, although rates of responding were low and decreased over sessions. Conclusions Across bottle-choice, binge intake, and operant procedures, female Long-Evans rats consumed more sucrose and responded at higher rates for sucrose. Although females also responded more for water, the vigor of responding did not explain the consistent sex difference in sucrose taking and seeking. The sex difference in sucrose taking was also not explained by sweet preference, as there was no sex difference in saccharin preference. These data provide a pre-clinical model to further evaluate sex differences in addiction behaviors and manipulations designed to reduce them.

Submitted as a Research Report to Biology of Sex Differences

Background: There are sex differences in addiction behaviors. To develop a pre-clinical animal model to investigate this, the present study examined sex differences in sucrose taking and seeking using LongEvans rats. Methods: Five experiments were conducted using separate groups of subjects. The first two examined sucrose or saccharin preference in two-bottle home cage choice tests. Experiment three assessed sucrose intake in a binge model with sucrose available in home cage bottles. Experiments four and five utilized operant-based procedures. In Experiment four rats responded for sucrose on fixed and progressive ratio (FR, PR) schedules of reinforcement over a range of concentrations of sucrose. A final component of experiment four was measuring seeking in the absence of sucrose challenged with the dopamine D1 receptor antagonist SCH23390. Experiment five assessed responding for water on FR and PR schedules of reinforcement. Results: When accounting for body weight, female rats consumed more sucrose than water; but there was no sex difference in saccharin preference over a range of saccharin concentrations. When accounting for body weight, females consumed more sucrose than males in the binge model, and only females increased binge intake over the 14 days of the study. Females responded at higher rates for sucrose under both FR and PR schedules of reinforcement. Females responded at higher rates in extinction (seeking); SCH23390 reduced sucrose seeking of both females and males. Females responded at higher rates for water on FR and PR schedules than males, although rates of responding were low and decreased over sessions. Conclusions: Across bottle-choice, binge intake, and operant procedures, female Long-Evans rats consumed more sucrose and responded at higher rates for sucrose. Although females also responded more for water, the vigor of responding did not explain the consistent sex difference in sucrose taking and seeking. The sex difference in sucrose taking was also not explained by sweet preference, as there was no sex difference in saccharin preference. These data corroborate with findings of sex differences in addiction behaviors in humans, providing a pre-clinical model to further evaluate sex differences in these behaviors and manipulations designed to reduce them.

Oral preload of calcium reduces food intake via enhanced PYY secretion in rats

IntroductionDietary calcium has been proposed to reduce appetite (or to enhance satiety) in human studies. However, underlying mechanisms are still unclear. In animal and cell studies, it has been demonstrated that activation of the calcium-sensing receptor induced secretion of anorexic gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells. In the present study, we tested the hypothesis that calcium suppresses appetite thorough enhanced gut hormone secretion, by using rats.Materials and MethodsMale Sprague Dawley rats were maintained by feeding a standard diet (AIN-93G, n = 6–8 per group). As calcium sources, calcium chloride, calcium carbonate, and calcium lactate were tested. These calcium salts were orally preloaded in fasted rats by using a feeding tube, and subsequent food intake was monitored until 24 hours. To assess conditioned taste aversion, saccharin preference test was conducted after conditioning with calcium or lithium chloride. To investigate involvements of gut hormones such as CCK, GLP-1, and peptide-YY (PYY), specific receptor antagonists for respective gut hormones were intraperitoneally injected just after oral preload of calcium, and then food intake was monitored. Portal blood samples were collected 15 or 30 min after oral preload of calcium for measurement of gut hormones by ELISA.Results and discussionAt the same dose of calcium (150 mg/kg), preload of calcium chloride reduced food intake for 4 hours compared to preload of the control solution (P < 0.05), while other compounds had minor effects on food intake. Saccharin preference ratio was only reduced by conditioning with lithium chloride (P < 0.01), but not by that with calcium compounds, indicating no conditional taste aversion was occurred by calcium. Suppressive effect of calcium chloride on food intake was partially reversed by pretreatment with a PYY receptor antagonist (BIIE0246) but not by that with a CCK- or a GLP-1 receptor antagonist. Portal PYY concentrations were higher in calcium chloride-treated rats than in the control rats (P < 0.05), 15 min after the preload and re-feeding. Changes in serum calcium concentrations were not observed by preload of calcium.These results suggest that oral preload of calcium chloride reduces subsequent food intake via enhanced PYY secretion in rats.

Parametric Characterization of a Taste Phenotype in Rats Selectively Bred for High Versus Low Saccharin Intake

Taste signals food quality and reflects energy status and associated processes. Occidental high- and low-saccharin consuming rats (HiS, LoS) have been selectively bred for nearly 60 generations on intake of 0.1% saccharin in a 23-h two-bottle test, as a tool for studying individual differences in taste and its correlates in the domains of feeding, defensive, and social behavior. The saccharin phenotype itself has not been well characterized until now. The present series of parametric studies examined suprathreshold saccharin concentration-intake functions (Experiment 1), saccharin preference threshold (Experiments 2A and 2B), and intra- and inter-sweetener carryforward effects (Experiments 2B, 3A–3D). Results indicate high stability in line differences in behavior toward saccharin and also line-specific mutability of intake of saccharin and certain other sweeteners. Methodological and conceptual implications are discussed.