PHARMACOLOGICAL VALIDATION OF THE CHRONIC MILD STRESS MODEL OF DEPRESSION

Chronic exposure to mild unpredictable stress has previously been foun d to depress the consumption of palatable sweet solutions, and this ef fect was reversed by chronic treatment with a variety of antidepressan t drugs. The present study reports three experiments examining the eff ects in this model of further antidepressant agents, a number of non-a ntidepressants, and some compounds of indeterminate clinical status. M ale Wistar rats were exposed sequentially to a variety of mild stresso rs, which continued throught the experiments. Drug treatments commence d after 3 weeks of stress, by which time intake of a 1% sucrose soluti on (measured in a 1-h weekly test) was significantly depressed. No dru g effects were seen after 1 week of treatment. Normal levels of sucros e drinking were seen following chronic (3-5 weeks) of treatment with t he antidepressants imipramine (10 mg/kg per day), brofaromine (20 mg/k g per day), and buspirone (5 mg/kg per day). Positive effects were als o seen following chronic treatment with atropine (1 mg/kg per day) and mepyramine (5 mg/kg per day). d-Amphetamine (1 and 3 mg/kg per day), the neuroleptics haloperidol and chlorprothixene (1 mg/kg per day), an d morphine (administered at doses rising to 110 mg/kg per day) were in effective; amphetamine (3 mg/kg) and morphine decreased sucrose intake in control animals. No inferences can be drawn from the effects of at ropine and mepyramine, which are of indeterminate clinical status; dat a from the other seven agents tested support the hypothesis that the c hronic mild stress model responds appropriately to antidepressant and non-antidepressant agents.