Hippocampal-Dependent Inhibitory Learning and Memory Processes in the Control of Eating and Drug Taking.

Abstract

As manifestations of excessive and uncontrolled intake, obesity and drug addiction have generated much research aimed at identifying common neuroadaptations that could underlie both disorders. Much work has focused on changes in brain reward and motivational circuitry that can overexcite eating and drug-taking behaviors. We suggest that the regulation of both behaviors depends on balancing excitation produced by stimuli associated with food and drug rewards with the behavioral inhibition produced by physiological "satiety" and other stimuli that signal when those rewards are unavailable. Our main hypothesis is that dysregulated eating and drug use are consequences of diet- and drug-induced degradations in this inhibitory power. We first outline a learning and memory mechanism that could underlie the inhibition of both food and drug-intake, and we describe data that identifies the hippocampus as a brain substrate for this mechanism. We then present evidence that obesitypromoting western diets (WD) impair the operation of this process and generate pathophysiologies that disrupt hippocampal functioning. Next, we present parallel evidence that drugs of abuse also impair this same learning and memory process and generate similar hippocampal pathophysiologies. We also describe recent findings that prior WD intake elevates drug self-administration, and the implications of using drugs (i.e., glucagon-like peptide- 1 agonists) that enhance hippocampal functioning to treat both obesity and addiction are also considered. We conclude with a description of how both WD and drugs of abuse could initiate a "vicious-cycle" of hippocampal pathophysiology and impaired hippocampal-dependent behavioral inhibition.