Augmentation of drug reward by chronic food restriction: behavioral evidence and underlying mechanisms.

摘要: Chronic food restriction and maintenance of low body weight have long been known to increase the self-administration motor-activating effects abused drugs. Using a lateral hypothalamic self-stimulation (LHSS) rate-frequency method, it is shown that chronic augments rewarding (i.e., threshold lowering) effect diverse drugs abuse. Further, attributed increased sensitivity neural substrate, rather than change in drug bioavailability or pharmacokinetics, because preserved when are injected directly into cerebral ventricle (intracerebroventricularly). The regimen reward also increases induction c-fos, by intracerebroventricular amphetamine, limbic forebrain dopamine (DA) terminal areas. possibility DA receptor function suggested findings direct agonists augmented restriction, behavioral amphetamine reversed an otherwise subthreshold dose D-1 antagonist. Initial studies receptor-mediated signal transduction, focused on D-2 receptor, suggest functional coupling between G-protein quinpirole-stimulated [(35)S]GTPgammaS binding) dorsal striatum. Unlike sensitization induced intermittent stress psychostimulant treatment, which persist indefinitely following induction, augmenting abates within 1 week restored ad libitum feeding gain. possible involvement endocrine hormones and/or 'feeding-related' neuropeptides, whose levels dynamically with depletion repletion adipose stores, therefore under investigation. tests limited acute treatments aimed at attenuating hypoinsulinemia, hypoleptinemia elevated corticosterone food-restricted rats. None these has attenuated restriction. While melanocortin agonist found enhance reward, receptors do not seem mediate Continuing investigations adiposity signals, neuropeptides dopaminergic transduction may further elucidate way abuse exploit mechanisms survival-related behavior, help explain high comorbidity eating disorders.