Convulsant activity of a non-peptidic δ-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats

Daniel C. Broom, Emily M. Jutkiewicz, John E. Folk, John R. Traynor, Kenner C. Rice, James H. Woods

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalPsychopharmacology
Volume164
Issue number1
DOIs
StatePublished - 2002

Keywords

  • (+)BW373U86
  • Convulsions
  • Depression
  • Forced swim assay
  • SNC80
  • δ-Opioid receptor

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Convulsant activity of a non-peptidic δ-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats'. Together they form a unique fingerprint.

Cite this