Convulsant activity of a non-peptidic δ-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats
- 1 October 2002
- journal article
- research article
- Published by Springer Nature in Psychopharmacology
- Vol. 164 (1) , 42-48
- https://doi.org/10.1007/s00213-002-1179-y
Abstract
Rationale. Non-peptidic δ-opioid receptor agonists possess antidepressant-like activity in the forced swim assay in the rat. These compounds have also previously been shown to possess convulsant properties in mice. Objective. The aim of the present study was to examine whether such convulsions occurred in rats and to investigate if δ-mediated convulsant activity was necessary for the mediation of δ-opioid agonist-induced antidepressant-like activity. Methods. The peripheral administration of δ-opioid receptor agonists to male Sprague-Dawley rats was followed by a period of observation for convulsant activity. Following this period and 60 min after δ-opioid agonist administration, rats were tested in the forced swim assay. Results. The non-peptidic δ-opioid receptor agonists (+)-4-[(R)-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide (SNC80) and (+)-4-[(R)-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide dihydrochloride [(+)BW373U86] both produced dose-dependent convulsant activity in rats and decreased immobility in the forced swim assay. The δ-opioid receptor antagonist naltrindole prevented the convulsant activity of (+)BW373U86 and its effects in the forced swim assay. This suggested a δ-opioid mechanism for both effects. Midazolam prevented convulsions but did not prevent activity in the forced swim assay. Rats tolerant to the convulsive effects of (+)BW373U86 still displayed antidepressant-like effects. Conclusion. δ-Mediated convulsions do occur in rats and can be prevented without affecting the δ-mediated effects in the forced swim assay. Therefore the convulsant activity of (+)BW373U86 and possibly other non-peptidic δ-agonists is not required for activity in the forced swim assay.Keywords
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