NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action.
The present study examined the effects of NIH 11082 ((-)-(1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride), a benzomorphan analogue, in the mouse tail-suspension, an assay used to detect anti-depressant agents. NIH 11082 significantly decreased immobility time during tail-suspension, with a comparable magnitude as the tricyclic anti-depressant desipramine. Importantly, NIH 11082 failed to elicit convulsions or other overt behavioral signs of toxicity. The delta-opioid receptor antagonist naltrindole (AD50=2.0 mg/kg), but not the non-selective mu-opioid receptor antagonist naltrexone or the kappa-opioid receptor antagonist nor-BNI, blocked the effects of NIH 11082 in the tail-suspension test. These results reinforce the notion that delta-opioid receptor agonists can produce significant effects in a behavioral model used to screen anti-depressant drugs.
Naidu
Pattipati S
PS
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, United States.
Lichtman
Aron H
AH
Archer
Carey C
CC
May
Everett L
EL
Harris
Louis S
LS
Aceto
Mario D
MD
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001575:Benzomorphans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D013623:Tail
C522796:5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride; D000928:Antidepressive Agents; D001575:Benzomorphans; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole