Modulation of rhythmical slow activity, long-term potentiation and memory by muscarinic receptor agonists.

ABSTRACT

We investigated the cholinergic modulation of hippocampal rhythmical slow activity (or theta activity), long-term potentiation and a behavioral memory task. The intravenous administration of the muscarinic receptor agonists, AF102B ((+/-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3') quinuclidine hydrochloride hemihidrate) and oxotremorine, induced rhythmical slow activity at doses of 1.0 mg/kg and 0.01 mg/kg, respectively. Long-term potentiation of population spike amplitude in the hippocampal CA1, which was induced by tetanic stimulation to the Schaffer collateral/commissural fiber, was increased by AF102B (1.0 mg/kg i.v.) and oxotremorine (0.01 mg/kg i.v.). Oral administration of AF102B and oxotremorine improved scopolamine-induced memory deficits in a passive avoidance task in mice at doses of 1.0 mg/kg and 0.2 mg/kg, respectively. The correspondence of the effective doses of muscarinic receptor agonists in these three experiments suggested the cholinergic correlation of rhythmical slow activity, long-term potentiation and memory.