GABA(B) receptor mechanism and imipramine-induced antinociception in ligated and non-ligated mice.
This study concerned the effects of GABA(B) receptor agents on imipramine-induced antinociception in ligated and non-ligated mice in hot-plate test. The data showed that different doses of morphine (3, 6 and 9 mg/kg) induced a dose-dependent antinociception in non-ligated or ligated mice. However, the opioid response was decreased in the ligated animals. Intracerebroventricular (i.c.v.) administration of imipramine (5, 10, 20 and 40 microg/mouse) did not induce antinociception in either non-ligated or ligated mice. However, the response induced in the ligated mice was less than that induced in the non-ligated animals. Intraperitoneal (i.p.) administration of imipramine (10, 20, 30 and 40 mg/kg) induced antinociception in both ligated and non-ligated animals. The responses to the drug were not significantly different in the two groups. Administration of baclofen either i.c.v. (0.125, 0.25 and 0. 5 microg/mouse) or i.p. (0.5, 1, 2 and 4 mg/kg) induced antinociception. The response to the drug was not significantly different in ligated and non-ligated mice. I.c.v. administration of a lower dose of baclofen (0.125 microg/mouse) with different doses of imipramine (2.5, 5 and 10 mg/kg) potentiates the response of imipramine. This effect was reduced by i.c.v. injection of GABA(B) receptor antagonist, CGP35348 [P-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid] (20 microg/mouse). The higher dose of antagonist (20 microg/mouse) also decreased the response induced by baclofen or imipramine. CGP35348 itself (2.5, 5, 10 and 20 microg/mouse) induced dose-dependent antinociception with no significant difference in the ligated and non-ligated mice. It is concluded that a GABA receptor mechanism(s) may modulate the antidepressant-induced antinociception.
Zarrindast
M
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Science, P.O. Box 13145-784, Tehran, Iran. zarinmr@ams.ac.ir
Valizadeh
S
S
Sahebgharani
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries
D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D009020:Morphine; C066430:CGP 35348; D001418:Baclofen; D007099:Imipramine