the role of gabab receptors in imipramine-induced antinociception in experimental model of neuropathic pain

this study was designed to investigate the role of gabab receptor agents on imipramine-induced antinociception in ligated and non-ligated mice using hot-plate test. the data showed that different doses of morphine (3, 6, and 9 mg/kg) induced a dose-dependent antinociception in ligated and non-ligated mice. however, the opioid response was decreased in ligated animals. intracerebroventricular (i.c.v.) administration of imipramine (5, 10, 20, and 40 µg/mouse) did not induce antinociception in either non-ligated or ligated mice. however, the induced response in the ligated mice was less than that induced in the non-ligated mice. intraperitoneal (i.p.) administration of imipramine (10, 20, 30, and 40 mg/kg) induced antinociception in both ligated and non-ligated mice. 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 µg/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. intracerebroventricular administration of a lower dose of baclofen (0.125 µg/mouse) with different doses of imipramine (2.5, 5, and 10 mg/kg) potentiated the response to imipramine. this effect was reduced by i.c.v. injection of gabab receptor antagonist, cgp35348 [p-(3-aminopropyl)-p-diethoxymethyl- phosphinic acid] at a dose of 20 µg/mouse. the higher dose of antagonist (20 µg /mouse) also decreased the response induced by baclofen or imipramine. cgp35348 itself (2.5, 5, 10, and 20 µg/mouse) induced a 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.