Role of cholinergic and GABAergic neuronal systems in cycloheximide-induced amnesia in mice

The role of cholinergic and GABAergic neuronal systems on the cycloheximide (CXM)-induced amnesia was investigated using the step-down-type passive avoidance task in mice. CXM (7.5-120 mg/kg, SC) given just after the training caused amnesia (indicated by short latency to step down from the platform on the grid floor) in the retention test conducted 24 hr later in a dose-dependent fashion. In the CXM (60 mg/kg)-treated mice, a choline esterase inhibitor, physostigmine (PHY; 0.125 and 0.25 mg/kg, IP), or GABA agonists, muscimol (1 and 2 mg/kg, IP) and baclofen (6 and 12 mg/kg, IP), given just after training markedly prolonged step down latency (SDL), indicating reversal of amnesia. The antiamnesic action of PHY (0.125 mg/kg) was almost completely antagonized by a central acetylcholine antagonist, scopolamine (3 mg/kg, SC), but not by a peripheral acetylcholine antagonist, butylscopolamine (3 mg/kg, SC). Furthermore, the antiamnesic action of muscimol (2 mg/kg) was reversed by GABA antagonists, picrotoxin (0.5 mg/kg, SC) and bicuculline (0.5 mg/kg, SC), while the effect of baclofen (12 mg/kg) was reversed by picrotoxin (0.5 mg/kg), but not by bicuculline (0.5 mg/kg). These results suggest that the dysfunction of cholinergic and GABAergic neuronal systems play an important role in the CXM-induced memory impairment on the passive avoidance task.