Abstract
According to the classification scheme of Kebabian and Calne, there are two types of dopamine (DA) receptors: D1 (activation of which causes increased cyclic AMP formation) and D2 (activation of which causes no increment in cyclic AMP). It is not clear what role the different receptors play in mediating motor behavior. Using drugs that act selectively at only one receptor site, we studied the effects of D1 and D2 receptor activation in two different models of parkinsonism--the rotating rat and the reserpinized mouse. Neither the D1 agonist nor the D2 agonist, given alone, could overcome reserpine akinesia, but together they restored locomotor activity. In rats with unilateral nigrostriatal lesions, both drugs induced a rotational response, each with a distinct temporal pattern. Pretreatment with alpha-methyl-paratyrosine (an inhibitor of DA synthesis) led to decrements in the rotational response induced by D2 agonists, but not that induced by D1 agonists. The mechanism by which these DA agonists induce motor activity is different; activation of both types of DA receptors seems to be necessary for normal motor behavior.
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