As an extension of the on going studies we are proposing to investigate further the antiparkinsonian efficacy of dopamine (DA) agonists and their interactions with pre and postsynaptic DA neuronal systems. Two animal models for Parkinsonism, namely rats with unilateral 6 OH-DA lesions of the nigro-striatal DA pathway, and monkeys with unilateral ventromedial tegmental lesions will be used to assess the in vivo potencies of various DA agonists. The potencies of the DA agonist in the behavioral tests in vivo will be compared with their binding potencies to DA receptor in vitro. To elucidate the mechanism of action of DA agonist we will investigate changes in the sensitivity of DA receptors following repeated administration of these drugs to animals with supersensitive DA receptors. Using pharmacological and biochemical criteria the multiple DA receptors will be characterized in the brains of rats and primates. Attempts will be made to correlate specific motor disturbances with changes in specific DA receptor systems. The possible interactions of central epinephrine (E) with DA in the hyp/thalamus and in its role in modulation of surgically induced parkinsonian like tremor or harmaline induced tremor will be investigated. The biochemical and morphological process involved in the regeneration of DA neurons will be studied by grafting substantia nigra into the denervated striatum.