Effect of intracerebroventricular injection of GABA receptor agents on morphine-induced antinociception in the formalin test.
In the present study, the effects of gamma-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 microg per rat) or baclofen (0.25, 0.5 and 1 microg 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 GABA(A) and GABA(B) 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 GABA(B) receptor agonist, through spinal and supraspinal opioid receptor mechanisms.
Mahmoudi
Mitra
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Zarrindast
Mohammad-Reza
MR
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D018682:GABA Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects*
D000701:Analgesics, Opioid; D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D005557:Formaldehyde; D009118:Muscimol; D009020:Morphine; C066430:CGP 35348; D001418:Baclofen; D001640:Bicuculline