Stress- and corticosteroid-induced modulation of the locomotor response tomorphine in rats

Stress alters the sensitivity to drugs of abuse and is, therefore, consider ed to be an important contributory factor to drug-seeking behaviour. There is only a limited amount of information available on stress-induced alterat ions in the behavioural response to opioids. We thus evaluated the influenc es of different stressors (restraint, handling, social defeat) on the locom otor effects induced by morphine. Further the importance of additional fact ors such as the number of stress events or the delay between stress and loc omotor testing on stress-induced alterations were evaluated. Since these mo dulatory effects of stress on the locomotor effects of morphine might be me diated via. the: release of endogenous corticosteroids we also tested the i nfluence of repeated intermittent and chronic administration of corticoster one (CORT) and the synthetic corticosteroid dexamethasone (DEX) on the loco motor response to morphine. Enhanced morphine-induced locomotor activity wa s observed in response to the repeated application (three times) of all str essors: restraint, handling and social defeat. An augmentation of the locom otor effects of a low (1 and 5 mg/kg) but not of a high dose (10 mg/kg) of morphine was seen after three, but not after one stress event. In addition, the repeated application of restraint stress (three times) resulted in an augmentation of morphine-induced locomotor stimulation 3 days, but not 1 or 10 days, after the last stress event. Similarly the repeated intermittent and chronic administration of corticosteroids, in particular of DEX, increa sed morphine's efficacy in stimulating locomotor activity. Our results show that stress is able to alter the locomotor stimulant effects of morphine i n rats-a phenomenon called stress-induced behavioural sensitization. Moreov er, these stress-induced alterations depend upon temporal factors such as n umber of stress events and the interval between stress and locomotor testin g. Further, stress-induced CORT-release seems to be involved in stress-indu ced behavioural sensitization to morphine. (C) 1999 Elsevier Science B.V. A ll rights reserved.