Objective: The aim of this study was to compare short- and long-term effects of levodopa on acetylcholinesterase activity in young and old rat brain striatum.

Background: The loss of dopamine (DA) content in Parkinson’s disease (PD) can be ameliorated by DA replacement therapy with levodopa. However, long-term treatment with levodopa of the patients, whilst improving the akinesia, also is accompanied by development of levodopa-induced dyskinesia. It is reported that DA depletion in PD blocks auto-inhibition of ACh release leading to the excessive ACh in the striatum. Conversely, DA replacement therapy decreases ACh in the striatum and increases activity of the direct striatal output pathway. Although the effects of levodopa on the ACh synthesizing enzymes have been extensively studied, no attempt has been made to evaluate the possible effect of levodopa on acetylcholinesterase (AChE), which inactivate ACh at synapses.

Methods: Male Wistar rats (3 and 30 months old) were injected(IP) with 1ml of a mixture of levodopa (10 mg/kg) and carbidopa (1mg/kg). Control animals were injected with 1 mL of saline. Rats were decapitated at 8 AM and the brain striatum was homogenized and centrifuged at 4°C. The activity of AChE was assayed in supernatant in the presence of acetylcholine and tetraisopropyl pyrophosphoramide. Dopamine was extracted from the same homogenates and the levels of DA were measured by HPLC.

Results: The striatal DA levels in young and aged rats were 53.11 ± 4.56 and 28.43 ± 3.13 nmol/ g wet wt. respectively. The AChE activities in corresponding homogenates were 32.41±2.76 and 58.08 ±3.34 μmol/min/mg protein. A single dose of the drug mixture increased DA content and decreased the enzyme activity in both ages, as measured 30 min post-injection, and returned to control values after 2h. When the drug mixture was injected for a period of 30 days and the animals were killed 24h after the last injection, a lower DA content and higher AChE activity were seen in both ages, although the changes were more pronounced in aged animals (p<0.005).

Conclusions: The result indicates that long-term treatment with levodopa in aged rat renders a dramatic rise in the striatal AChE, leading to imbalance Ach/DA levels in straitum. Ultimately, AChE might be consider as therapeutic targets for combating motor complications affecting PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-associated-effects-of-levodopa-administration-on-striatal-acetylcholinesterase-activity/