The present study evaluated the effects of combined alpha2-antagonist (atipamezole) and anticholinesterase (tetrahydroaminoacridine, THA) or muscarinic agonist (pilocarpine) treatments on the high voltage spindle (HVS) activity in aged rats. On their own, high doses of THA (3 mg/kg), pilocarpine (3 mg/kg) and atipamezole (3 mg/kg) suppressed HVS activity. Low doses of THA (1 mg/kg), pilocarpine (1 mg/kg) and atipamezole (1 mg/kg) did not suppress HVS activity. Combinations of low doses of atipamezole and THA or pilocarpine suppressed HVS activity. Our results suggest that 1) the administration of alpha2-antagonist blocked the age-related deficit of thalamocortical activation, 2) a combination of alpha2-antagonist and a cholinergic drug may more effectively stabilize age-related HVS activity than either of the treatments alone.