Differential behavioral tolerance to the δ-opioid agonist SNC80 ((+)-4-[(αR)-α-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl] -(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in Sprague-Dawley rats

Emily M. Jutkiewicz, Sarah T. Kaminsky, Kenner C. Rice, John R. Traynor, James H. Woods

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Nonpeptidic δ-opioid agonists produce a number of behaviors, such as antidepressant-like effects, locomotor stimulation, antinociception, and convulsions. To consider this class of compounds as potential therapeutics for humans, the effects δ-opioid agonists after repeated administration must be evaluated. Therefore, the present study investigated the effects of repeated δ-opioid agonist, SNC80 ([(+)-4-[(αR)-α-[(2S,5R)-2,5-dimethyl- 4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)-methyl]-N,N-diethylbenzamide), administration on its antidepressant-like effects in the forced swim test, locomotor activity, and convulsions in male Sprague-Dawley rats. Tolerance developed rapidly to the convulsive and locomotor-stimulating effects of SNC80 but not to the antidepressant-like effects. In addition, tolerance was evaluated at the level of the receptor-G protein interaction by measuring 5′-O-(3-[35S]thio)triphosphate binding in brains from rats that were pretreated with SNC80. With various exposure durations to SNC80, some brain regions demonstrated tolerance at different times, suggesting that adaptations in the δ-opioid system may occur during agonist exposure. Overall, the lack of observable tolerance to the antidepressant-like effects of SNC80 indicates that this class of compounds has potential as a novel antidepressant therapy.

Original languageEnglish (US)
Pages (from-to)414-422
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume315
Issue number1
DOIs
StatePublished - Oct 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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