Physostigmine induces in rats a phenomenon resembling long-term potentiation

The study dealt with a phenomenon similar to long-term potentiation of hippocampal population spikes that was observed with a high dose of physostigmine given to rats. The population spikes in the dentate granule cells in anesthetized rats were enhanced to 135, 152 and 167% of the control level 60, 120 and 240 min after the administration of physostigmine (0.1 mg/kg i.v.), respectively. The time course of the enhancement was consistent with that of blocked paired pulse inhibition by physostigmine in anesthetized rats. Such a block of paired pulse inhibition was seen at the observation of the long-term potentiation phenomenon to tetanic stimulation (100 Hz, 2 s). Perfusion of physostigmine (10(-5) M) or bicuculline (10(-6) M) elicited second spikes following the population spikes in CA1 pyramidal cells. The second spikes elicited by physostigmine were decreased by scopolamine (10(-6) M) and muscimol (5 x 10(-7) M), while those caused by bicuculline were decreased by muscimol but not by scopolamine. It is suggested that physostigmine induces a long-term potentiation-like phenomenon through a transient, abrupt increase in excitability and the subsequent block of recurrent GABAergic inhibition in the hippocampus.