An anti-immobility effect of exogenous corticosterone in mice.
Although traditionally considered to be etiological factors in depression, corticosteroids have been shown to exert an acute antidepressant action under some conditions. To investigate the mechanism of this effect, the present experiment sought to develop an animal model of it in mice using the repeated forced swim procedure. Corticosterone or desmethylimipramine was administered in the drinking water before, during or after repeated daily forced swims or a tail suspension test. Glucocorticoid and mineralocorticoid receptor involvement were assessed by coadministration of RU486 or spironolactone. Plasma corticosterone and fos expression in the paraventricular nucleus of the hypothalamus and piriform cortex were also measured in the treated animals. Corticosterone, given either before/during or after repeated swim, was found to produce a rapid reduction of immobility that was greater than that produced by desmethylimipramine given by the same route and dose and for the same duration. There was a nonsignificant tendency toward this effect in the tail suspension test. RU486 failed to block the effect but results with spironolactone were ambiguous. Plasma corticosterone was elevated in an inverted U-shaped fashion by the hormone treatment. Fos expression in response to the last swim was blunted in the paraventricular hypothalamus but enhanced in the piriform cortex. It is concluded that short-term treatment with corticosterone has a marked antidepressant effect in the mouse repeated forced swim test and merits further consideration as a short-term therapeutic agent in low doses. The hormone may act by suppression of neural activity in central stress circuits leading to a disinhibition of regions involved in active behavioral coping.
Stone
Eric A
EA
Department of Psychiatry, New York University School of Medicine, 550 First Ave, New York, NY 10016, USA. eric.stone@med.nyu.edu
Lin
Yan
Y
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003891:Desipramine; D003345:Corticosterone