Involvement of the opioid system in the anxiolytic effect of diazepam in mice.
In the present study, the anticonflict effect of diazepam was significantly abolished by pretreatment with naloxone, beta-funaltrexamine or nor-binaltorphimine but not naltrindole, using a Vogel-type conflict paradigm in mice. However, naloxone alone had a significant proconflict effect, and beta-funaltrexamine alone tended to produce a proconflict effect. Spontaneous drinking behavior was not affected by treatment with diazepam and nor-binaltorphimine. In addition, nor-binaltorphimine had no effect on diazepam-induced motor incoordination, hypothermia or anticonvulsant action, respectively. Moreover, the stable dynorphin analog E2078 ([N-methyl-Tyr1, N-alpha-methyl-Arg7-D-Leu8]dynorphin A-(1-8) ethylamide) and the highly selective kappa-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide++ + methanesulfonate hydrochloride) produced a significant anticonflict effect, which was completely antagonized by pretreatment with nor-binaltorphimine. These findings suggested that the kappa-opioid system may play an important role in the anxiolytic effect of benzodiazepine and the regulation of anxiety.
Tsuda
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Suzuki
T
T
Misawa
M
M
Nagase
H
H
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003220:Conflict, Psychological; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000819:agonists
D018712:Analgesics, Non-Narcotic; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C061285:E 2078; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D003975:Diazepam