CHRONIC VARIABLE STRESS ENHANCES THE STIMULATORY ACTION OF A LOW-DOSEOF MORPHINE - REVERSAL BY DESIPRAMINE

Adult male rats were exposed to a chronic variable stress treatment, a n animal model of depression, with or without concurrent daily adminis tration of desipramine. Animals given chronic and variable stress were submitted daily to a different stressor following an injection of eit her saline or desipramine (5 mg/kg, i.p.), whereas control animals wer e unmanipulated except for the injection process. One day after the la st event of the chronic procedure, control and stressed animals were a dministered saline or morphine (0.75 or 1.5 mg/kg, i.p.) and their loc omotion assessed for 90 min. In an additional experiment, 24 h after t he last stressor, stressed and control rats were challenged with eithe r saline or one of two higher doses (behaviorally suppressant) of morp hine (5 and 10 mg/kg, i.p.). A significantly greater increase in locom otor activity following a low dose (1.5 mg/kg) of morphine was observe d in chronically stressed rats as compared to control rats. This poten tiated locomotor response to morphine in stressed rats was prevented b y desipramine pretreatment. The chronic and variable stress treatment did not modify the sedative response to the high doses of morphine. Th ese data support the suggestion that a chronic and variable stress pro cedure results in sensitization to the stimulant effect of opioid stim ulation, and that pretreatment with the antidepressant agent desiprami ne blocks the development of this sensitization.