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

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, 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Ltd
ISSN
0014-2999
DOI
10.1016/0014-2999(96)00219-1
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

European Journal of PharmacologyElsevier

Published: Jun 20, 1996

References

  • Naloxone blocks the antianxiety but not the motor effects of benzodiazepines and pentobarbital: experimental studies and literature review
    Agmo, A.; Galvan, A.; Heredia, A.; Morales, M.
  • Chlordiazepoxide attenuates response suppression induced by corticotropin-releasing factor in the conflict test
    Britton, K.T.; Morgan, J.; Rivier, J.; Vale, W.; Koob, G.F.
  • Corticotropin releasing factor and amphetamine exaggerate partial agonist properties of benzodiazepine antagonist Ro 15-1788 in the conflict test
    Britton, K.T.; Lee, G.; Koob, G.F.
  • Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze
    Privette, T.H.; Terrian, D.M.
  • Effects of benzodiazepine and GABA antagonists on anticonflict effects of antianxiety drug injected into the rat amygdala in a water-lick suppression test
    Shibata, S.; Yamashita, K.; Yamamoto, E.; Ozaki, T.; Ueki, S.
  • Differential effects of naloxone against the diazepam-induced release of behavior in rat in three aversive situations
    Soubrie, P.; Jobert, A.; Theibot, M.H.
  • A simple reliable conflict procedure for testing anti-anxiety agents
    Vogel, J.R.; Beer, B.; Clody, D.E.

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