title: Pharmacological validation of the chronic mild stress model of depression.
abstract: Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions, and this effect was reversed by chronic treatment with a variety of antidepressant drugs. The present study reports three experiments examining the effects in this model of further antidepressant agents, a number of non-antidepressants, and some compounds of indeterminate clinical status. Male Wistar rats were exposed sequentially to a variety of mild stressors, which continued throught the experiments. Drug treatments commenced after 3 weeks of stress, by which time intake of a 1% sucrose solution (measured in a 1-h weekly test) was significantly depressed. No drug effects were seen after 1 week of treatment. Normal levels of sucrose drinking were seen following chronic (3-5 weeks) of treatment with the antidepressants imipramine (10 mg/kg per day), brofaromine (20 mg/kg per day), and buspirone (5 mg/kg per day). Positive effects were also 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), and morphine (administered at doses rising to 110 mg/kg per day) were ineffective; amphetamine (3 mg/kg) and morphine decreased sucrose intake in control animals. No inferences can be drawn from the effects of atropine and mepyramine, which are of indeterminate clinical status; data from the other seven agents tested support the hypothesis that the chronic mild stress model responds appropriately to antidepressant and non-antidepressant agents.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Papp
authors.forename: E
authors.initials: E
authors.lastname: Moryl
authors.forename: P
authors.initials: P
authors.lastname: Willner
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D002491:Central Nervous System Agents