title: Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion.
abstract: Repeated exposures to stress sensitize motor and addictive effects of drugs of abuse. Recently, it has been shown that stress-induced behavioral sensitization depends on the secretion of glucocorticoids. We investigated if sensitization of dopamine-dependent effects of psychostimulants and opioids was influenced by glucocorticoid. Sensitization of the dopaminergic response to drugs is considered the neural substrate of behavioral sensitization and has been implicated in vulnerability to drug abuse. Dopamine-dependent effects of psychostimulants and opioids were evaluated by injecting either amphetamine into the nucleus accumbens (10 micrograms/side) or morphine into the ventral tegmental area (VTA) (1 microgram/side). The locomotor response to psychostimulants and opioids injected in these brain areas depends on the mesencephalic dopaminergic transmission. Drug-induced locomotion was compared in male rats in which corticosterone secretion was either in +tct or experimentally suppressed by an adrenalectomy associated with a substitutive treatment reproducing basal levels of the hormone. Eight days of food restriction (80% of the initial body weight) were used as a stressor. Suppression of stress-induced corticosterone secretion abolished food restriction-induced sensitization of the locomotor effects of intra-accumbens amphetamine and intra-VTA morphine. This effect was corticosterone dependent since the restoration of corticosterone levels in the range of those induced by stress totally reinstates sensitization. Our results suggest that glucocorticoids control stress-induced sensitization by changing the sensitivity of the mesencephalic dopaminergic transmission to drugs of abuse. Since dopaminergic effects of drugs are related to their addictive properties, secretion of glucocorticoids may be one of the factors determining the enhanced vulnerability to drugs observed in stressed subjects.
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D007267:Injections; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000503:physiopathology
chemical_list: D015259:Dopamine Agents; D009294:Narcotics; D009020:Morphine; D000661:Amphetamine; D004298:Dopamine; D003345:Corticosterone