Reframing appetitive reinforcement learning and reward valuation as effects mediated by hippocampal-dependent behavioral inhibition.

Traditional theories of neuroeconomics focus on reinforcement learning and reward value. We propose here a novel reframing of reinforcement learning and motivation that includes a hippocampal-dependent regulatory mechanism which balances cue-induced behavioral excitation with behavioral inhibition. This mechanism enables interoceptive cues produced by respective food or drug satiety to antagonize the ability of excitatory food- and drug-related environmental cues to retrieve the memories of food and drug reinforcers, thereby suppressing the power of those cues to evoke appetitive behavior. When the operation of this mechanism is impaired, ability of satiety signals to inhibit appetitive behavior is weakened because the relative balance between inhibition and simple excitation is shifted toward increased retrieval of food and drug memories by environmental cues. In the present paper, we (1) describe the associative processes that constitute this mechanism of hippocampal-dependent behavior inhibition; (2) describe how a prevailing obesity-promoting diet and drugs of abuse produce hippocampal pathophysiologies that can selectively impair this inhibitory function; and (3) propose how glucagon-like peptide 1 (GLP-1), an incretin hormone that is recognized as an important satiety signal, may work to protect the hippocampal-dependent inhibition. Our perspective may add to neuroscientific and neuroeconomic analyses of both overeating and drug abuse by outlining the role of hippocampal-dependent memory processes in the control of both food and drug seeking behaviors. In addition, this view suggests that consideration should be given to diet- and drug induced hippocampal pathophysiologies, as potential novel targets for the treatment of dysregulated energy and drug intake.