EFFECTS OF MUSCARINIC RECEPTOR AGONISTS AND ANTICHOLINESTERASE DRUGS ON HIGH-VOLTAGE SPINDLES AND SLOW WAVES

The effects of muscarinic agonists (AF102B, pilocarpine, oxotremorine) and anticholinesterases (physostigmine, tetrahydroaminoacridine) were investigated on the incidence of thalamically generated rhythmic high voltage spindles and on scopolamine (0.2 mg/kg)-induced neocortical slow wave activity (i.e. increased sum amplitude value of the 1-20 Hz band in a quantitative electroencephalography (qEEG) analysis). AF102B and pilocarpine decreased high voltage spindles and scopolamine increased sum amplitude values at 3 and 9 mg/kg, but not at 1 mg/kg. Oxotremorine was less potent than AF102B or pilocarpine in suppressing high voltage spindles. Oxotremorine had no effect on the scopolamine-induced qEEG changes. Tetrahydroaminoacridine decreased high voltage spindles at 1, 3 and 9 mg/kg and slow waves at 9 mg/kg. Physostigmine decreased high voltage spindles and slow waves at 0.12 and 0.36 mg/kg. Based on the present results we propose that agonists possessing muscarinic M1 receptor activity are effective in decreasing high voltage spindles and scopolamine-induced slow wave activity, but agonists showing predominant muscarinic M2 receptor activity may be less effective in decreasing high voltage spindles and slow waves. Furthermore, tetrahydroaminoacridine decreased high voltage spindles at doses lower than those required to decrease scopolamine-induced slow waves. Physostigmine decreased high voltage spindles and slow waves over the same dose range. This result may indicate that non-cholinergic mechanisms are involved in the tetrahydroaminoacridine-induced decrease in high voltage spindles.