Nonpeptidic δ-opioid receptor agonists reduce immobility in the forced swim assay in rats

被引:144
作者
Broom, DC
Jutkiewicz, EM
Folk, JE
Traynor, JR
Rice, KC
Woods, JH
机构
[1] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Psychol, Ann Arbor, MI 48109 USA
[3] NIDDK, Bethesda, MD 20892 USA
关键词
delta opioid receptor; depression; forced swim assay; SNC80; (+)BW373U86;
D O I
10.1016/S0893-133X(01)00413-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study examined the effect of opioid receptor agonists in the rat forced swim assay. The delta-opioid receptor agonists SNC80 ((+)-4-[(aR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N- diethylbenzamide) and (+)BW373U86 ((+)-[1(S*),2alpha,5beta]-4-[[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl] (3-hydroxyphenyl)methyl]-N,N-diethyl-benzamide dihydrochloride) produced a decrease in immobility indicating an antidepressant-like effect. At antinociceptive doses, neither the kappa-opioid selective agonist C1977 (5R-(5alpha,7alpha,8beta)-N-methyl-N-[7-(1-pyrrolidinyl-1- oxaspiro[4,5]dec-8-yl]-4-benzofuranacetamide) showed a change in immobility that was identifiable by dose, nor were changes in immobility seen with morphine. A delta-opioid mechanism of action in the forced swim assail was likely since naltrindole prevented the effects of both delta-agonists. When compared to desipramine and fluoxetine, SNC80 was more active with a single dose whereas both desipramine and fluoxetine produced greater effects with subchronic dosing (3 doses). All three compounds were active when administered before the initial swim exposure. SNC80 was, however, more effective following a single dose than by subchronic administration demonstrating both a fast onset of activity and potential tolerance, Thus, delta-agonists differ from typical antidepressants in the forced swim assay. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
引用
收藏
页码:744 / 755
页数:12
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