Exposure to chronic mild stress alters thresholds for lateral hypothalamic stimulation reward and subsequent responsiveness to amphetamine.
Chronic mild stress in rodents has been proposed to model some of the environmental factors that contribute to the induction of depressive disorders in humans. This model is based on the hypothesis that chronic mild stress induces a change in brain reward function that resembles the symptomatology of major depression, namely, a decrease in responsiveness to rewarding stimuli. The purpose of the first experiment was to investigate whether chronic mild stress affects brain reward function as measured by alterations in lateral hypothalamic self-stimulation behavior in rats. Exposure to chronic mild stress induces a reduction in body weight which might affect brain reward function on its own. Therefore, the potential contribution of a reduction in body weight to the chronic mild stress-induced alterations in brain reward function was examined in a separate group of food-restricted rats. Thresholds for lateral hypothalamic self-stimulation were slightly but significantly lowered in animals exposed to chronic mild stress, indicating an enhancement of stimulation reward efficacy. Food restriction had no effect on brain reward function. The second experiment examined the interaction between prior exposure to chronic mild stress or food restriction and responsiveness to a pharmacological challenge, amphetamine, that enhances brain reward function. Acute administration of amphetamine produced a greater enhancement of lateral hypothalamic self-stimulation reward in animals exposed to chronic stress relative to non-stressed and food-restricted animals. Taken together, the present findings indicate that chronic mild stress sensitizes the neural substrates that mediate both lateral hypothalamic stimulation and psychostimulant drug reward. These findings support the hypothesis that prior exposure to stress affects the vulnerability for drug-taking behavior by increasing the positive reinforcing properties of drug of abuse.
Lin
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Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torry Pines Road, La Jolla, CA 92037, USA. dlin@arenapharm.com
Bruijnzeel
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Schmidt
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Markou
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D000661:Amphetamine / Q000494:pharmacology; D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002908:Chronic Disease; D005508:Food Deprivation; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012201:Reward; D012653:Self Stimulation; D013312:Stress, Physiological / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000697:Central Nervous System Stimulants; D000661:Amphetamine