title: Extinction-induced "despair" in the water maze, exploratory behavior and fear: effects of chronic antidepressant treatment.
abstract: In former studies, we found evidence for the hypothesis that withdrawal of negative reinforcement presents a major source for stress and despair. Specifically, the removal of a hidden platform in the water maze induced extinction of previously reinforced escape behavior and behavioral immobility, indicative of "despair", which also correlated with indices of fear. Here, we tested the effects of antidepressants on extinction in the water maze, and expected that such drugs would attenuate the rate of extinction of a conditioned place preference (CPP) and also any emotionally relevant behavior that is induced by the loss of reinforcement, such as immobility. Adult male Wistar rats were trained to escape onto a hidden platform for 10 days. Daily treatment with desipramine hydrochloride (DMI, 10mg/kg) or fluoxetine (FLX, 10 mg/kg) commenced 1 day before the first of 11 extinction trials without the platform, administered 48 h apart, and continued thereafter, as the rats were tested in an open field and elevated-plus maze. As compared to controls, DMI increased the resistance-to-extinction of CPP, attenuated immobility, and increased wall climbing behavior. In the open field, DMI reduced activity levels, but was without effect on traditional fear parameters in the elevated-plus maze. FLX, by contrast, increased immobility during the extinction trials and fear in the elevated-plus maze. The withdrawal of reinforcement induced "despair" that was alleviated by the noradrenaline reuptake inhibitor DMI. The effects of the selective serotonin reuptake inhibitor FLX on immobility and fear may be explained in terms of its side effect profile.
authors.affiliation: Institute of Physiological Psychology and Center for Biological and Medical Research, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulz
authors.forename: Tim
authors.initials: T
authors.lastname: Buddenberg
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
mesh_terms: D000339:Affect; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004924:Escape Reaction; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D003891:Desipramine