Involvement of the opioid system in the anxiolytic effect of diazepam in mice

• Published in: European journal of pharmacology 1996-06, Vol.307 (1), p.7-14
• Main Authors: Tsuda, Makoto, Suzuki, Tsutomu, Misawa, Miwa, Nagase, Hiroshi
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Anti-Anxiety Agents - antagonists & inhibitors; Anti-Anxiety Agents - pharmacology; Anticonflict effect; Anticonvulsants - pharmacology; Biological and medical sciences; Body Temperature - drug effects; Conflict (Psychology); Diazepam; Diazepam - antagonists & inhibitors; Diazepam - pharmacology; Drug Interactions; Dynorphins - pharmacology; Male; Medical sciences; Mice; Mice, Inbred Strains; Motor Activity - drug effects; Mouse; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Neuropharmacology; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Opioid - drug effects; Receptors, Opioid - physiology; Receptors, Opioid, kappa - agonists; Vogel-type conflict test; κ-Opioid receptor agonist
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(96)00219-1

In the present study, the anticonflict effect of diazepam was significantly abolished by pretreatment with naloxone, β-funaltrexamine or nor-binaltorphimine but not naltrindole, using a Vogel-type conflict paradigm in mice. However, naloxone alone had a significant proconflict effect, and β-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-Tyr 1, N-α-methyl-Arg 7, d-Leu 8]dynorphin A-(1–8) ethylamide) and the highly selective κ-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 κ-opioid system may play an important role in the anxiolytic effect of benzodiazepines and the regulation of anxiety.