Affiliation:
1. Departments of Psychiatry, Biochemistry and Molecular Pharmacology, New York University School of Medicine, 435 East 30th Street, New York, NY 10016, United States
Abstract
Energy homeostasis is achieved, in part, by metabolic signals that regulate the incentive motivating
effects of food and its cues, thereby driving or curtailing procurement and consumption. The neural underpinnings
of these regulated incentive effects have been identified as elements within the mesolimbic dopamine pathway.
A separate line of research has shown that most drugs with abuse liability increase dopamine transmission in
this same pathway and thereby reinforce self-administration. Consequently, one might expect shifts in energy
balance and metabolic signaling to impact drug abuse risk. Basic science studies have yielded numerous examples
of drug responses altered by diet manipulation. Considering the prevalence of weight loss dieting in Western
societies, and the anorexigenic effects of many abused drugs themselves, we have focused on the CNS and behavioral
effects of food restriction in rats. Food restriction has been shown to increase the reward magnitude of diverse
drugs of abuse, and these effects have been attributed to neuroadaptations in the dopamine-innervated nucleus
accumbens. The changes induced by food restriction include synaptic incorporation of calcium-permeable
AMPA receptors and increased signaling downstream of D1 dopamine receptor stimulation. Recent studies suggest
a mechanistic model in which concurrent stimulation of D1 and GluA2-lacking AMPA receptors enables
increased stimulus-induced trafficking of GluA1/GluA2 AMPARs into the postsynaptic density, thereby increasing
the incentive effects of food, drugs, and associated cues. In addition, the established role of AMPA receptor
trafficking in enduring synaptic plasticity prompts speculation that drug use during food restriction may more
strongly ingrain behavior relative to similar use under free-feeding conditions.
Funder
National Institute on Drug Abuse
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
11 articles.
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