Age Related Effects of Levodopa on Rat Brain Striatal Acetylcholinesterase

Abstract

Long-term treatment of Parkinson's disease (PD) with levodopa is accompanied by dyskinesia. Alteration in striatal acetylcholine signaling is partly responsible, but the involved mechanisms have yet to be determined. This study aimed to compare repeated levodopa treatment on dopamine (DA) content and acetylcholinesterase (AChE) activity in the young and old rat brain striatum. Male Wistar rats (3 and 30 months old) were injected with a mixture of levodopa + carbidopa (10 + 1 mg/kg). Control animals received normal saline only. Rats were killed and brain striatum was homogenized and centrifuged at 4 degrees C. AChE activity was assayed in the supernatant and DA was extracted from the homogenate and measured by high performance liquid chromatography with electrochemical detection. The levels of DA in young and aged rats were 53.1 +/- 4.5 and 28.4 +/- 3.1 nmol/g wet weight tissue respectively. AChE activity in corresponding supernatant was 32.4 +/- 2.7 and 58.1 +/- 3.3 mu mol/min/mg protein. A single dose of the drug mixture increased DA content and decreased AChE activity in both ages. When the drug mixture was injected daily for a period of 30 days, a lower DA content and a higher AChE activity were observed, though the changes were more pronounced in the aged animals. The result indicates that long-term treatment with levodopa + carbidopa in aged rat renders a dramatic rise in the striatal AChE, leading to imbalance ACh/DA levels in the striatum. It is concluded that AChE might be considered as a therapeutic target for combating levodopa-induced dyskinesia affecting PD patients.