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

Article date: 1988/10/1

PubMed ID: 2854264

Journal name: Pharmacology, biochemistry, and behavior (ISSN: 0091-3057)


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.

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Author List: Nabeshima T, Noda Y, Itoh K, Kameyama T

Publication Types: Journal Article

Substances mentioned in the article: Receptors, Cholinergic; Receptors, GABA-A; Picrotoxin; Muscimol; Butylscopolammonium Bromide; Scopolamine Hydrobromide; Cycloheximide; Physostigmine; Baclofen; Bicuculline;

Mesh terms: Amnesia/chemically induced; Animals; Avoidance Learning/drug effects; Baclofen/pharmacology; Bicuculline/pharmacology; Butylscopolammonium Bromide/pharmacology; Cycloheximide/pharmacology; Male; Mice; Muscimol/pharmacology; Physostigmine/pharmacology; Picrotoxin/pharmacology; Receptors, Cholinergic/drug effects; Receptors, GABA-A/drug effects; Scopolamine Hydrobromide/pharmacology;

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