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Effect of intracerebroventricular injection of GABA receptor agents on morphine-induced antinociception in the formalin test

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Mohammad-Reza Zarrindast

Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran; zarinmr{at}ams.ac.ir

In the present study, the effects of -aminobutyric acid (GABA) receptor agonists and antagonists on antinociception induced by morphine in the formalin test were investigated in rats. Intraperitoneal (i.p.) injection of different doses of morphine (1, 3, 6 and 9 mg/kg) and intracerebroventricular (i.c.v.) injection of different doses of muscimol (0.5, 1 and 2 µg per rat) or baclofen (0.25, 0.5 and 1 µg per rat) induced a dose-related antinociception in the both first and second phases of the formalin test. The responses induced by muscimol or baclofen in both phases were reduced by bicuculline or CGP35348 [p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid], respectively. Bicuculline alone has produced antinociception in the second phase and CGP35348 alone has had antinociception in both phases of the formalin test. Morphine in combination with different doses of muscimol or baclofen did not elicit potentiation. The opioid receptor antagonist naloxone reduced the response induced by muscimol in the second phase and baclofen in both phases of the formalin test. It may be concluded that central GABAA and GABAB receptor stimulation induces antinociception in the formalin test. However, the antinociception induced by GABA receptor agonists may be mediated partly through supraspinal opioid receptor mechanisms and, for the GABAB receptor agonist, through spinal and supraspinal opioid receptor mechanisms.

Key Words: antinociception • formalin test • GABA receptor agonists and antagonists • rats

Journal of Psychopharmacology, Vol. 16, No. 1, 85-91 (2002)
DOI: 10.1177/026988110201600108


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