Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats.
The present study examined the effect of opioid receptor agonists in the rat forced swim assay. The delta-opioid receptor agonists SNC80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) and (+)BW373U86 ((+)-[1(S*),2 alpha,5 beta]-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 CI977 (5R-(5 alpha,7 alpha,8 beta)-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 assay 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.
Broom
Daniel C
DC
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.
Jutkiewicz
Emily M
EM
Folk
John E
JE
Traynor
John R
JR
Rice
Kenner C
KC
Woods
James H
JH
D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007103:Immobilization / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009294:Narcotics / Q000494:pharmacology / Q000627:therapeutic use; D009930:Organic Chemicals; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology; D013550:Swimming / Q000502:physiology
D001549:Benzamides; D009294:Narcotics; D009930:Organic Chemicals; D010879:Piperazines; D017465:Receptors, Opioid, delta; C016005:morphine-like compounds (non-peptide); C083877:BW 373U86; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide