GABAergic system and imipramine-induced impairment of memory retention in rats.

In this study, the influence of GABAergic agents, imipramine and their interactions on memory retention have been investigated. Intracerebroventricular (i.c.v.; 1-6 microg/rat) or intraperitoneal (i.p.; 5-40 mg/kg) injection of imipramine decreased memory retention. i.c.v. administration of GABA receptor agonists baclofen and muscimol also reduced memory retention. The combination of i.p. or i.c.v. injection of imipramine with a low dose of muscimol (1 microg/rat, i.c.v.) induced a higher decrease in memory retention. The higher dose of GABA(B) receptor antagonist CGP35348 [p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid] (10 microg/rat) increased memory retention by itself, and decreased the response induced by baclofen or imipramine. Bicuculline (1, 2 and 4 microg/rat, i.c.v.) tends to increase memory retention by itself. Furthermore, bicuculline in same doses reduced the response induced by muscimol or imipramine, but it did not show interaction with the latter drugs. It is concluded that the GABA(B) receptor mechanism is involved in memory impairment induced by imipramine.