The effects of single and repeated doses of maprotiline, oxaprotiline and its enantiomers on foot-shock induced fighting in rats

Abstract

Foot-shock induced fighting behavior (SIF) in rats was tested after single and repeated dose-treatment (10 mg/kg IP twice daily for 10 days) of maprotiline, oxaprotiline and of(+)- and (−)-enantiomers of oxaprotiline. Marked facilitation of SIF was observed after repeated but not single administration of all drugs including the NA-uptake inactive (−)-enantiomer of oxaprotiline. No enhancement of SIF was seen after multiple dose-treatment with promethazine, an antihistaminic, or atropine. The mechanism of the facilitation of SIF induced by antidepressants maprotiline and oxaprotiline as well as by its enantiomers is unclear. The clear-cut dissociation of the effect of (+)- and (−)-oxaprotiline on the rate of NA-disappearance, but their similar enhancing effect on SIF challenges the assumption of a primary importance of central NA-system in this behavior. By contrast, the increase in jumping behavior recorded additionally to SIF, seems to be a great extent dependent on NA-uptake inhibiting properties of tested drugs.