Pharmacologic effects of L-dopa are not closely linked temporally to striatal dopamine concentration.

In an attempt to gain insight into the mechanism of the "long-term response" to L-dopa in parkinsonians, we studied the temporal relationship between turning behavior and striatal dopamine (DA) levels after L-dopa administration to rats with unilateral nigral lesions. Turning behavior peaked at 30 minutes (9.0 +/- 1.5 turns per rat per minute), diminished in intensity, reached a new peak (10.8 +/- 1) at 3 hours, and persisted for 280 minutes after L-dopa administration. In contrast, dopamine levels in the striatum ipsilateral to the lesion peaked at 20 minutes and returned to control levels by 90 minutes after L-dopa administration. These data suggest that behaviors elicited by an increase in brain (striatal) dopamine levels may persist long after the dopamine concentration has returned to control levels.