(+/-)Baclofen sensitive scopolamine-induced short-term memory deficits in mice.

Possible involvement of GABA receptor systems in scopolamine-induced short-term memory deficits was investigated using latency of mice to reach shock-free zone (SFZ) and number of mistakes (descents) the animal made in 15 min as parameters for acquisition and retention of memory in passive avoidance paradigm. Atropine (1-5 mg/kg), scopolamine (0.1-0.5 mg/kg) but not pirenzepine (5-20 mg/kg) caused disruption of memory. GABA (50, 75 and 100 mg/kg) showed retention enhancing effects in scopolamine-treated and untreated animals but GABA agonist progabide (5-20 mg/kg) did not affect any of the parameter significantly. GABAA agonist, muscimol (0.05 and 0.1 mg/kg) and GABAB agonist, (+/-)baclofen (0.25, 0.5 and 1 mg/kg) and (-)baclofen (0.25 and 0.5 mg/kg) also displayed memory enhancing action. Whereas, GABAA antagonist, bicuculline produced hind limb rigidity, GABAB antagonist, CGP 35348 did not show any effect per se, but reversed the (+/-)baclofen-induced delay in latency, without affecting retention enhancing action of (+/-)baclofen. Combined administration of subeffective dose of GABA (50 mg/kg) and (+/-)baclofen (0.25 mg/kg), showed a significant improvement in acquisition and retention. However, the effect of GABA (100 mg/kg) on acquisition was reversed by bicuculline (2 mg/kg) and by CGP 35348 (100 mg/kg) while improving retention. The present study extends support to the cholinergic concept in cognitive performance and provide an evidence for the influence of GABAergic (particularly GABAB) modulation in scopolamine-induced learning and memory deficits in mice.