Motoric sensitization and levodopa accumulation after chronic levodopa treatment in an animal model of Parkinson's disease

Abstract

One month after rats were subjected to unilateral injections of either 6-hydroxydopamine (6-OHDA) or vehicle into the midbrain tegmentum, they were given daily injections of either saline or levodopa (10 mg/kg and 1 mg/kg carbidopa) for 30 days. On the first and last day of treatment the spontaneous behavior of the rats was evaluated with a video image analysis system that detected directional movement asymmetries. Although vehicle-injected rats exhibited very little movement asymmetry, the 6-OHDA rats were strongly asymmetric. On day 1, both saline and levodopa-treated 6-OHDA rats exhibited rotational movement directed toward the dopamine-deficient hemisphere. On day 30 of treatment, however, the chronic levodopa group displayed a complete reversal and exaggeration of the rotational bias, and all asymmetric movement was directed toward the dopamine-intact hemisphere. Thus chronic levodopa treatment shifted behavioral dominance from the intact to the dopamine-denervated hemisphere. Subsequent biochemical measurement of dopamine and levodopa in striatal and limbic tissue samples indicated that chronic levodopa treatment did not alter dopamine tissue concentrations but did substantially increase levodopa concentrations, both in the dopamine-denervated striatum and in limbic tissue. This increased levodopa loading in brain with chronic levodopa treatment occurring in 6-OHDA rats but not in vehicle-injected rats that were given the same levodopa regimen. This selectivity in the effect of chronic levodopa treatment to the 6-OHDA rats appeared to rule out the possibility of peripheral metabolic factors for the levodopa accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)