BEHAVIORAL EFFECTS OF -METHYLTYROSINE AFTER PRIOR DEPLETION OF BRAIN CATECHOLAMINES

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, and Department of Pharmacology, Michigan State University, East Lansing, Michigan

Small doses of -methyltyrosine (-MT; 50 mg/kg) and reserpine (0.5 mg/kg), which by themselves had little influence on conditioned avoidance behavior and locomotor activity of rats, greatly disrupted these responses when administered together. This combination also reduced brain stores of norepinephrine (NE) and dopamine (D) more than either drug alone. Three days after a larger dose of reserpine (2 mg/kg), rats recovered from the behavioral depression but the brain levels of NE and D were still very low. At this time -MT (50 mg/kg) markedly impaired avoidance responding, rotarod performance and motor activity, and also further reduced NE and D. The depressant effects of subsequent -MT injections diminished as the brain stores of NE and D returned toward control values (7-14 days after reserpine). -MT also depressed behavioral responses in animals pretreated with tetrabenazine and Ro 4-1284; the time course of these behavioral effects again paralleled that of the reduced brain content of NE and D. -MT did not impair behavior when administered to rats just recovering from central depression induced by drugs which do not alter brain catecholamine levels (fluphenazine, pentobarbital or urethane). These results support the proposal that -MT-induced behavioral effects relate to a lack of NE and/or D in the brain.