STRESS-INDUCED SENSITIZATION AND GLUCOCORTICOIDS .1. SENSITIZATION OFDOPAMINE-DEPENDENT LOCOMOTOR EFFECTS OF AMPHETAMINE AND MORPHINE DEPENDS ON STRESS-INDUCED CORTICOSTERONE SECRETION

Repeated exposures to stress sensitize motor and addictive effects of drugs of abuse, Recently, it has been shown that stress-induced behavi oral sensitization depends on the secretion of glucocorticoids, We inv estigated if sensitization of dopamine-dependent effects of psychostim ulants and opioids was influenced by glucocorticoids. 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 opio ids were evaluated by injecting either amphetamine into the nucleus ac cumbens (10 mu g/side) or morphine into the ventral tegmental area (VT A) (1 mu g/side). The locomotor response to psychostimulants and opioi ds injected in these brain areas depends on the mesencephalic dopamine rgic transmission, Drug-induced locomotion was compared in male rats i n which corticosterone secretion was either in +tct or experimentally suppressed by an adrenalectomy associated with a substitutive treatmen t reproducing basal levels of the hormone, Eight days of food restrict ion (80% of the initial body weight) were used as a stressor, Suppress ion of stress-induced corticosterone secretion abolished food restrict ion-induced sensitization of the locomotor effects of intra-accumbens amphetamine and intra-VTA morphine, This effect was corticosterone dep endent 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 c hanging 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 o f the factors determining the enhanced vulnerability to drugs observed in stressed subjects.