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Midazolam attenuates the antinociception induced by d-serine or morphine at the supraspinal level in rats.

Abstract：

:Our recent study has shown that the intracerebroventricular administration of d-serine, an endogenous and selective agonist for the glycine site of the N-methyl-d-aspartate receptor, alone or in combination with morphine, leads to the potentiation of antinociception on the tail-flick response. Although there is a variety of information concerning the effects of benzodiazepines on opioid-induced antinociception, little is known about the effect of benzodiazepines on the N-methyl-d-aspartate receptor agonist-induced antinociception. To clarify the analgesic interactions among the benzodiazepine/GABA(A), N-methyl-d-aspartate and opioid receptors at the supraspinal level, we investigated the effects of intracerebroventricular administration of midazolam, a benzodiazepine receptor agonist, on the antinociception evoked by the intracerebroventricular application of d-serine or morphine. The intracerebroventricular administration of midazolam alone produced hyperalgesia on the tail-flick response in a benzodiazepine receptor antagonist, flumazenil-reversible manner. The antinociception induced by the intracerebroventricular application of d-serine or morphine was attenuated by the intracerebroventricular administration of midazolam. In addition, this inhibitory effect of midazolam on the antinociception of d-serine or morphine was antagonized by the intracerebroventricular administration of flumazenil. Together with the facts that d-serine and midazolam act as selective agonists for the glycine site of the N-methyl-d-aspartate receptor and benzodiazepine/GABA(A) receptor, respectively, these observations suggest a functional interaction between the NMDA and benzodiazepine/GABA(A) receptors in the regulation of antinociception at the supraspinal level.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Ito K,Yoshikawa M,Maeda M,Jin XL,Takahashi S,Matsuda M,Tamaki R,Kobayashi H,Suzuki T,Hashimoto A

doi

10.1016/j.ejphar.2008.02.068

subject

Has Abstract

pub_date

2008-05-31 00:00:00

pages

139-44

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)00262-8

journal_volume

586

pub_type

杂志文章

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Midazolam attenuates the antinociception induced by d-serine or morphine at the supraspinal level in rats.