Effects of benztropine on ketamine-induced behaviors in Cebus monkeys

Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor a ntagonist, causes a schizophrenic-like psychosis in normal volunteers and e xacerbates psychotic symptoms in patients with schizophrenia. Recent work h as shown that ketamine and other NMDA antagonists affect a range of behavio rs in nonhuman primates, particularly those associated with motor and menta l function such as attention and perception. Several lines of study also su ggest that NMDA antagonists interact with cholinergic mechanisms. The effec ts of benztropine, an anticholinergic agent, on ketamine-induced behaviors were evaluated in a double-blind randomized test design in 20 Cebus monkeys . Benztropine (0.05, 0.1 and 0.25 mg/kg, i.m.) was injected 1 hour before k etamine (2.5 and 5.0 mg/kg, i.m.) administration. Behaviors scored for 90 m inutes after ketamine administration included salivation, dystonia and reac tivity to external stimuli. Benztropine almost completely blocked ketamine- induced hypersalivation, and partially ameliorated the dystonia syndrome by 50%, but did not affect ketamine-induced decreased reactivity to external stimuli. These results suggest that cholinergic mechanisms only moderately influence ketamine-induced central nervous system effects of motor dysfunct ion, and may not play a substantive role in the ketamine-induced deficit of reactivity to external stimuli, which involves a complex interaction of me ntal functions such as attention and perception, as well as motor behavior. (C) 2001 Lippincott Williams & Wilkins.