MODIFICATION OF LEVODOPA RESPONSES BY DEPRENYL (SELEGILINE) - AN ELECTROPHYSIOLOGICAL AND BEHAVIORAL-STUDY IN THE RAT RELEVANT TO PARKINSONS-DISEASE

From using in vitro intracellular recordings from mesencephalic neuron s and monoamine-depleted rats, we report that the functions of levodop a in the brain are greatly enhanced and prolonged by high doses of the monoamine oxidase (MAO) inhibitor deprenyl. Dopaminergic neurons were hyperpolarized and inhibited by levodopa application. These effects o f levodopa were largely potentiated by pretreatment with nonselective doses of deprenyl. Furthermore, when locomotor activity induced by lev odopa was examined on a rodent model of Parkinson's disease, pretreatm ent of the animals with nonselective doses of deprenyl caused an enhan cement of the antiparkinsonian action of levodopa The great increase i n levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine precursor with a higher dosage of the MAO inhibitor, to reduce effectively the daily levodopa requirements in Parkinson's dise ase patients.