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Journal of Pharmacology And Experimental Therapeutics, Vol. 153, Issue 3, 412-419, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics

ALTERATIONS IN BEHAVIOR AND BRAIN CATECHOLAMINE LEVELS IN RATS TREATED WITH agr-METHYLTYROSINE

R. H. RECH 1, H. K. BORYS 1, and K. E. MOORE 1

1 Department of Pharmacology and Toxicology, Dartmouth Medical School,Hanover, New Hampshire

agr-Methyltyrosine (agr-MT) has been proposed to cause central nervous depression by blocking synthesis of brain catecholamines. However, interpretation of these reports is complicated by the toxicity of this drug. In the present study, the effects of agr-MT on behavior and brain catecholamine content of rats were examined with doses and routes of administration that did not cause toxicity. Behavioral tests consisted of conditioned avoidance responding, rotarod performance and spontaneous locomotor activity. Single intraperitoneal injections of agr-MT caused marked loss of avoidance responding only in doses that were toxic. Subcutaneous injections were only slightly effective in depressing behavior because of the poor absorption of agr-MT. Oral (200 mg/kg) or multiple intraperitoneal injections (3 x 50 mg/kg) of agr-MT impaired avoidance responding, rotarod performance and spontaneous locomotor activity without producing obvious toxic effects. The content of agr-MT in the brain and depletion of brain norepinephrine and dopamine bothexhibited a time course similar to that of the behavioral depression.

Submitted on January 28, 1966
Accepted on March 29, 1966




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