Inhibition of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.

Abstract:

:This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity as measured in mice, and the morphine-induced hyperactivity was inhibited dose-dependently by the administration of the GABA(A) agonist, muscimol (0.3, 0.5 and 1.0 mg kg(-1) i.p.). However, daily repeated administration of morphine caused the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.). The administration of muscimol inhibited the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.) in mice that had received chronic administration of morphine. Postsynaptic dopamine receptor supersensitivity, as shown by the enhanced ambulatory activity after administration of apomorphine (2 mg kg(-1) s.c.), also developed in reverse-tolerant mice. Muscimol also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited via the activation of GABA(A) receptors.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Yoon IS,Kim HS,Hong JT,Lee MK,Oh KW

doi

10.1159/000064345

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

204-9

issue

4

eissn

0031-7012

issn

1423-0313

pii

64345

journal_volume

65

pub_type

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