The effects of cholinergic drugs on rat neocortical high-voltage spindles in ketanserin-treated rats

To investigate the roles of the cholinergic system and 5-HT2 receptors in the modulation of thalamocortical oscillations, we studied the effects of systemic (s.c.) administration of anticholinesterases (physostigmine, tetrahydroaminoacridine) and muscarinic acetylcholine receptor agonists (pilocarpine, oxotremorine) on spontaneous thalamically generated rhythmic neocortical high-voltage spindles in adult rats pretreated with either saline or ketanserin, a 5-HT2 receptor antagonist. Ketanserin at 20.0 mg/kg increased the number of high-voltage spindles. In saline-treated rats, tetrahydroaminoacridine 3.0 and 9.0 mg/kg was able to decrease high-voltage spindles, whereas in ketanserin 20.0 mg/kg-treated rats only the highest dose of tetrahydroaminoacridine (9.0 mg/kg) decreased high-voltage spindles. Both doses of physostigmine, 0.12 and 0.36 mg/kg, decreased high-voltage spindles in both saline and ketanserin 20.0 mg/kg-treated rats. Lower doses of tetrahydroaminoacridine (1.0 mg/kg) and physostigmine (0.06 mg/kg) were ineffective in both saline- and ketanserin 20.0 mg/kg-treated rats. Pilocarpine 3.0 mg/kg and oxotremorine 0.1 and 0.9 mg/kg decreased high-voltage spindles in saline-treated rats. However, in rats treated with ketanserin 20.0 mg/kg, only the lower doses of pilocarpine (0.3 and 1.0 mg/kg) and oxotremorine (0.03 mg/kg) were able to decrease the high-voltage spindles. The results suggest that activation of the cholinergic system and activation of 5-HT2 receptors have additive effects in the suppression of thalamocortical oscillations and related neocortical high-voltage spindles in rats, thus maintaining effective information processing in thalamocortical networks.