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Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats.
Psychopharmacology (Berl). 2002 Oct; 164(1):42-8.P

Abstract

RATIONALE

Non-peptidic delta-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 delta-mediated convulsant activity was necessary for the mediation of delta-opioid agonist-induced antidepressant-like activity.

METHODS

The peripheral administration of delta-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 delta-opioid agonist administration, rats were tested in the forced swim assay.

RESULTS

The non-peptidic delta-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 delta-opioid receptor antagonist naltrindole prevented the convulsant activity of (+)BW373U86 and its effects in the forced swim assay. This suggested a delta-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

delta-Mediated convulsions do occur in rats and can be prevented without affecting the delta-mediated effects in the forced swim assay. Therefore the convulsant activity of (+)BW373U86 and possibly other non-peptidic delta-agonists is not required for activity in the forced swim assay.

Authors+Show Affiliations

Department of Pharmacology, University of Michigan Medical School, 1301 Medical Science Research Building III, Ann Arbor, MI 48109-0632, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12373418

Citation

Broom, Daniel C., et al. "Convulsant Activity of a Non-peptidic Delta-opioid Receptor Agonist Is Not Required for Its Antidepressant-like Effects in Sprague-Dawley Rats." Psychopharmacology, vol. 164, no. 1, 2002, pp. 42-8.
Broom DC, Jutkiewicz EM, Folk JE, et al. Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. Psychopharmacology (Berl). 2002;164(1):42-8.
Broom, D. C., Jutkiewicz, E. M., Folk, J. E., Traynor, J. R., Rice, K. C., & Woods, J. H. (2002). Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. Psychopharmacology, 164(1), 42-8.
Broom DC, et al. Convulsant Activity of a Non-peptidic Delta-opioid Receptor Agonist Is Not Required for Its Antidepressant-like Effects in Sprague-Dawley Rats. Psychopharmacology (Berl). 2002;164(1):42-8. PubMed PMID: 12373418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. AU - Broom,Daniel C, AU - Jutkiewicz,Emily M, AU - Folk,John E, AU - Traynor,John R, AU - Rice,Kenner C, AU - Woods,James H, Y1 - 2002/07/30/ PY - 2001/12/28/received PY - 2002/05/26/accepted PY - 2002/10/10/pubmed PY - 2003/1/8/medline PY - 2002/10/10/entrez SP - 42 EP - 8 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 164 IS - 1 N2 - RATIONALE: Non-peptidic delta-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 delta-mediated convulsant activity was necessary for the mediation of delta-opioid agonist-induced antidepressant-like activity. METHODS: The peripheral administration of delta-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 delta-opioid agonist administration, rats were tested in the forced swim assay. RESULTS: The non-peptidic delta-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 delta-opioid receptor antagonist naltrindole prevented the convulsant activity of (+)BW373U86 and its effects in the forced swim assay. This suggested a delta-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: delta-Mediated convulsions do occur in rats and can be prevented without affecting the delta-mediated effects in the forced swim assay. Therefore the convulsant activity of (+)BW373U86 and possibly other non-peptidic delta-agonists is not required for activity in the forced swim assay. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12373418/Convulsant_activity_of_a_non_peptidic_delta_opioid_receptor_agonist_is_not_required_for_its_antidepressant_like_effects_in_Sprague_Dawley_rats_ L2 - https://dx.doi.org/10.1007/s00213-002-1179-y DB - PRIME DP - Unbound Medicine ER -