EFFECT OF -METHYL DOPA ON THE RESERPINE-INDUCED SUPPRESSION OF MOTOR ACTIVITY AND THE CONDITIONED AVOIDANCE RESPONSE

¹ Departments of Pharmacology and Psychiatry, The University of Chicago, Chicago, Illinois

The reserpine-induced suppression of the conditioned avoidance response in rats was partially and temporarily reversed by the injection of -methyl-dihydroxyphenylalanine (-methyl dopa) (200 mg/kg). -Methyl dopa also reversed the reserpine-induced suppression of motor activity in rats. Occurring concomitantly with the increase in motor activity was a rise in brain -methylated amines. The brain -methylated amine levels, however, declined more slowly than did the motor activity. Both the increase in motor activity and the amount of -methylated amines formed were dependent on the dose of -methyl dopa administered. To determine the role of the -methylated amines and -methyl dopa in the reversal of the reserpine-induced suppression of motor activity, RO-4-4602, an aromatic amino acid decarboxylase inhibitor, was administered. Reserpine-pretreated animals, receiving RO-4-4602 (400 mg/kg) before -methyl dopa (400 mg/kg), showed a lower brain content of -methylated amines and a lower level of motor activity than animals not treated with the decarboxylase inhibitor. The brain levels of -methyl dopa, however, were not changed. This would support the hypothesis that the -methylated amines could act as false transmitters in the brain. For all doses of -methyl dopa, the motor activity of animals pretreated with reserpine was markedly greater than that of animals pretreated with vehicle. A hypothesis was proposed to explain the difference in motor activity between the latter two groups on the basis of the present data. Received for publication October 28, 1968.