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.