EFFECTS OF NICOTINE ON NEOCORTICAL ELECTRICAL-ACTIVITY IN RATS

The present study investigates the effects of acute and repeated nicot ine i.p. treatment on cortical EEG activity. Nicotine at 0.3 and 0.9 m g/kg, but not at 0.1 mg/kg, decreased high voltage spindles (HVSs). Ni cotine at 2.7 mg/kg suppressed HVSs completely. Mecamylamine, a nicoti nic cholinergic antagonist, increased HVSs at 5 and 7.5 mg/kg. Nicotin e blocked the HVS induction induced by mecamylamine. Mecamylamine at 1 .25 mg/kg antagonized the HVS suppressing action of nicotine at 0.3 mg /kg. The muscarinic cholinergic antagonist, scopolamine (0.2 mg/kg), i ncreased the 1 to 20 Hz amplitude sum value, and this increase was blo cked to some extent by the highest dose of nicotine (2.7 mg/kg). Howev er, nicotine did not block the effect of a higher scopolamine (2.0 mg/ kg) dose on the sum amplitude values. Mecamylamine at 2.5 and 7.5 mg/k g blocked the effect of nicotine at 2.7 mg/kg on the EEG sum amplitude values in scopolamine (0.2 mg/kg)-treated rats. The peripherally acti ng nicotinic and muscarinic cholinergic antagonists, hexamethonium and scopolamine methylbromide, had no effect on spectral EEG and HVS valu es. In quisqualic acid nucleus basalis-lesioned rats, a frontal cortic al choline acetyltransferase depletion (-72%) and slowing of the EEG w as observed. Nicotine could not restore EEG activity in nucleus basali s-lesioned rats. After repeated (10 days, three injections/day) admini stration of nicotine, no tolerance to the effects of either nicotine ( 0.9 mg/kg) on spontaneously occuring HVSs or nicotine (2.7 mg/kg) on t he EEG change induced by scopolamine was observed. The present results show that nicotinic receptor stimulation desynchronizes neocortical E EG activity in normal animals, but this action disappears in basal for ebrain-lesioned animals. Therefore, it is likely that the effects of n icotine in reversing EEG and behavioral abnormalities observed in Alzh eimer's disease may be limited if the basal forebrain cell loss is ext ensive.