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.
Keywords: Obesity, drug abuse, learning, memory, hippocampus, Western diet, vicious-cycle model.
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