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.
European Journal of Pharmacology – Elsevier
Published: Jun 20, 1996
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