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

Abstract
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.
AuthorsM Tsuda, T Suzuki, M Misawa, H Nagase
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 307 Issue 1 Pg. 7-14 (Jun 20 1996) ISSN: 0014-2999 [Print] Netherlands
PMID8831097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics, Non-Narcotic
  • Anti-Anxiety Agents
  • Anticonvulsants
  • Narcotic Antagonists
  • Peptide Fragments
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • E 2078
  • norbinaltorphimine
  • Naltrexone
  • Dynorphins
  • Diazepam
Topics
  • Analgesics, Non-Narcotic (pharmacology)
  • Animals
  • Anti-Anxiety Agents (antagonists & inhibitors, pharmacology)
  • Anticonvulsants (pharmacology)
  • Body Temperature (drug effects)
  • Conflict, Psychological
  • Diazepam (antagonists & inhibitors, pharmacology)
  • Drug Interactions
  • Dynorphins (pharmacology)
  • Male
  • Mice
  • Mice, Inbred Strains
  • Motor Activity (drug effects)
  • Naltrexone (analogs & derivatives, pharmacology)
  • Narcotic Antagonists (pharmacology)
  • Peptide Fragments (pharmacology)
  • Receptors, Opioid (drug effects, physiology)
  • Receptors, Opioid, kappa (agonists)

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