Chronic variable stress enhances the stimulatory action of a low dose of morphine: reversal by desipramine.
Adult male rats were exposed to a chronic variable stress treatment, an animal model of depression, with or without concurrent daily administration of desipramine. Animals given chronic and variable stress were submitted daily to a different stressor following an injection of either saline or desipramine (5 mg/kg, i.p.), whereas control animals were unmanipulated except for the injection process. One day after the last event of the chronic procedure, control and stressed animals were administered saline or morphine (0.75 or 1.5 mg/kg, i.p.) and their locomotion assessed for 90 min. In an additional experiment, 24 h after the last stressor, stressed and control rats were challenged with either saline or one of two higher doses (behaviorally suppressant) of morphine (5 and 10 mg/kg, i.p.). A significantly greater increase in locomotor activity following a low dose (1.5 mg/kg) of morphine was observed in chronically stressed rats as compared to control rats. This potentiated locomotor response to morphine in stressed rats was prevented by desipramine pretreatment. The chronic and variable stress treatment did not modify the sedative response to the high doses of morphine. These data support the suggestion that a chronic and variable stress procedure results in sensitization to the stimulant effect of opioid stimulation, and that pretreatment with the antidepressant agent desipramine blocks the development of this sensitization.
Molina
V A
VA
Department of Psychology, Binghamton University, State University of New York 13902-6000.
Heyser
C J
CJ
Spear
L P
LP
D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000523:psychology*
D009020:Morphine; D003891:Desipramine