Effects of nicotine on cortical high voltage spindles in rats.

Cholinergic systems have been shown to modulate 6-10 Hz immobility-related cortical spike wave discharges (high voltage spindles-HVS) in rats. This study reports that activation of central nicotinic receptors inhibits HVS identified from cortical EEG recordings. Nicotine (0.19-1.9 mumol/kg i.p.) significantly reduced the summed duration of HVS bursts during 20 min of waking immobility. The nicotinic antagonist mecamylamine (5.0 mumol/kg i.p.) blocked the effect of nicotine (0.62 mumol/kg i.p.) without itself significantly affecting HVS. At higher doses, mecamylamine (15.0 and 25.0 mumol/kg i.p.) increased HVS activity. Dimethylphenylpiperazinium (0.62-6.2 mumol/kg i.p.), a nicotinic agonist which does not cross the blood-brain barrier, did not affect HVS, consistent with the idea that the effect of nicotine on HVS is due to an action in the central nervous system. Cotinine, the major metabolite of nicotine, did not affect HVS at doses similar to or higher than those tested for nicotine. Cotinine also did not block the effect of nicotine, indicating that this metabolite does not interfere with the modulatory effect of nicotine on HVS. These results suggest a role for nicotinic regulation of the neuronal substrates involved in the generation of HVS.