SEROTONERGIC MODULATION OF ANTICHOLINERGIC EFFECTS ON COGNITION AND BEHAVIOR IN ELDERLY HUMANS

Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or toget her with the serotonin mixed agonist/antagonist m-chlorophenylpiperazi ne (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each recei ved five separate pharmacologic challenges (placebo, ondansetron, scop olamine, scopolamine + ondansetron, and scopolamine + m-CPP). Cognitiv e, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in cer tain cognitive, behavioral, and physiological measures were significan tly exaggerated by the addition of m-CPP. Scopolamine's cognitive effe cts were unaffected by ondansetron at the dose tested, nor did ondanse tron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influen ce cholinergic neurotransmission. The changes associated with the comb ination of scopolamine and m-CPP do not appear to be secondary to simp le pharmacokinetic alterations and suggest a complex interaction betwe en the cholinergic and serotonergic systems centrally.