Nucleus accumbens AMPA receptor trafficking upregulated by food restriction: an unintended target for drugs of abuse and forbidden foods

There is a high rate of comorbidity between eating disorders and substance abuse, and specific evidence that weight-loss dieting can increase risk for binge pathology, rebound excessive weight gain, and initiation and relapse to drug abuse. The present overview discusses basic science findings indicating that chronic food restriction induces dopamine conservation, compensatory upregulation of D-1 dopamine receptor signaling, and synaptic incorporation of calcium-permeable glutamatergic AMPA receptors in nucleus accumbens. Evidence is presented which indicates that these neuroadaptations account for increased incentive effects of food, drugs, and associated environments during food restriction. In addition, these same neuroadaptations underlie upregulation of sucrose-induced and psychostimulant-induced trafficking of AMPA receptors to the nucleus accumbens postsynaptic density, which may be a mechanistic basis of enduring maladaptive behavior.