Effects of muscarinic receptor agonists and anticholinesterase drugs on high voltage spindles and slow waves

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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 M 1 receptor activity are effective in decreasing high voltage spindles and scopolamine-induced slow wave activity, but agonists showing predominant muscarinic M 2 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.