ACTIVATION OF ACETYLCHOLINE-RECEPTORS AND 5-HT2 RECEPTORS HAVE ADDITIVE EFFECTS IN THE SUPPRESSION OF NEOCORTICAL HIGH-VOLTAGE SPINDLES IN AGED RATS

We investigated if activation of the muscarinic or nicotinic acetylcho line receptors and serotonin (5-hydroxytryptamine; 5-HT) subtype 2 rec eptors would have additive or synergistic effects on the suppression o f thalamocortically generated rhythmic neocortical high-voltage spindl es (HVSs) in aged rats, The 5-HT2 receptor antagonist, ketanserin, at a moderate dose (5 mg/kg) prevented the ability of a muscarinic acetyl choline receptor agonist, (oxotremorine 0.1 mg/kg), and a nicotinic ac etylcholine receptor agonist (nicotine 0.1 mg/kg), to decrease HVSs. A t a higher dose (20 mg/kg), ketanserin completely blocked the decrease in HVSs produced by moderate doses of muscarinic acetylcholine recept or agonists (pilocarpine I mg/kg and oxotremorine 0.1 mg/kg), and by a high dose of nicotine (0.3 mg/kg), though not that produced by high d oses of pilocarpine (3 mg/kg) and oxotremorine (0.9 mg/kg). Tile abili ty of a 5-HT2 receptor agonist, +/-)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) (0.1-1.0 mg/kg), to suppress HVSs was non-significa ntly modulated by the nicotinic acetylcholine receptor antagonist, mec amylamine (1-15 mg/kg), and the muscarinic acetylcholine receptor anta gonist, scopolamine (0.03-0.3 mg/kg). The effects of the drugs on beha vioral activity could be separated from their effects on HVSs. The res ults suggest that activation of the muscarinic or nicotinic acetylchol ine receptors plus 5-HT2 receptors has additive effects in the suppres sion of thalamocortical oscillations in aged rats.