THE EFFECTS OF LIRAGLUTIDE ON THE LEARNED CONTROL OF APPETITIVE BEHAVIOR

The GLP-1 analogue liraglutide has recently received attention as being a potential therapeutic treatment for obesity as it has been associated with decreases in consumption, body adiposity, and body weight. The purpose of the present set of experiments was to assess the mechanisms underlying the ability for liraglutide to alter appetitive behavior in both male and female rats. Experiment 1 found that 12d of peripheral liraglutide injections (10 μg/kg) was able to suppress body fat accumulation and increase hippocampal-dependent inhibition. Liraglutide injections did not alter responding on hippocampal-independent excitation. Findings from Experiment 1 did not vary by sex or diet consumed. Experiment 2 found that 10 μg/kg of liraglutide was able to alter body composition without inducing taste avoidance in both male and female rats. Experiment 3 extended these findings by showing that a single pre-diet exposure to 10 μg/kg of liraglutide can blunt the effectiveness of later chronic injections at suppressing body fat accumulation. Changes in body adiposity were correlated with changes in GLUT-1 levels in the hippocampus. GLUT-1 expression was upregulation in rats chronically injected with 10 μg/kg of liraglutide, but this upregulation did not occur when rats were pre-treated with a single dose of liraglutide. Experiment 4 used the parameters identified in Experiments 2 and 3 and extended findings from Experiment 1. Liraglutide did not alter responding on a hippocampal-independent simple discrimination task, even in rats that showed changes in hippocampal-dependent behavior. Taken together, the findings from this dissertation indicate that, in doses that suppress body fat gain, liraglutide does not globally alter hippocampal-independent excitation or discrimination, but rather specifically enhances hippocampal-dependent behavioral inhibition. These results provide evidence for the conceptualization that liraglutide acts to suppress appetitive behavior via hippocampal-dependent associative mechanisms.