Dopamine receptor changes in response to prolonged treatment with L-dopa.

Unilateral lesions of the nigro-striatal dopamine (DA) pathway induced contralateral rotations to apomorphine, increased (3H)-spiroperidol binding and enhanced the sensitivity of striatal adenylate cyclase to DA stimulation. Prolonged L-dopa administration counteracted the increased density of (3H)-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to DA and decreased the inhibitory effect of opiates on this enzyme. The apomorphine-induced contralateral rotations were also strongly potentiated. On the contrary the binding of (3H)-SCH-23390 was affected neither by DA nerve degeneration nor by chronic L-dopa treatment. These results suggest that DA-D1 and DA-D2 receptors are differently affected by prolonged L-dopa treatment. The biochemical changes of DA-D1 receptors associated with adenylate cyclase seem to be correlated with the enhanced behavioural responses to apomorphine and could be a consequence of a decreased opiate inhibitory tone on the enzyme. The increased supersensitivity of the DA-D1 receptors may play a role in the clinical changes seen in parkinsonian patients following chronic use of L-dopa.