Short ReportsEffects of benztropine on ketamine-induced behaviors in Cebus monkeysShiigi, Y.a; Casey, D.E.bAuthor Information a Research Laboratories, Welfide Corporation, Iruma, Saitama, Japan and b Mental Illness Research, Education and Clinical Center, VA Medical Center, Portland; Oregon Regional Primate Research Center, Beaverton; and Departments of Psychiatry and Neurology, Oregon Health Sciences University, Portland, Oregon, USA Correspondence to Daniel E. Casey, Mental Health Division (P3MHDC), VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97201, USA. E-mail: [email protected] Received 27 June 2000 Revised 20 May 2001 Accepted 20 May 2001 Behavioral Pharmacology: July 2001 - Volume 12 - Issue 4 - p 293-298 Buy Abstract Ketamine, a noncompetitive N -methyl- d -aspartate (NMDA) glutamate receptor antagonist, causes a schizophrenic-like psychosis in normal volunteers and exacerbates psychotic symptoms in patients with schizophrenia. Recent work has shown that ketamine and other NMDA antagonists affect a range of behaviors in nonhuman primates, particularly those associated with motor and mental function such as attention and perception. Several lines of study also suggest that NMDA antagonists interact with cholinergic mechanisms. The effects 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 ketamine (2.5 and 5.0 mg/kg, i.m.) administration. Behaviors scored for 90 minutes after ketamine administration included salivation, dystonia and reactivity 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 dysfunction, and may not play a substantive role in the ketamine-induced deficit of reactivity to external stimuli, which involves a complex interaction of mental functions such as attention and perception, as well as motor behavior. © 2001 Lippincott Williams & Wilkins, Inc.