Suppressive effect of <scp>L</scp>‐dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6‐hydroxydopamine

TLDR

Since the introduction of L‑dopa for Parkinson’s disease, concerns have arisen that it may accelerate dopamine neuron degeneration. The study examined whether chronic L‑dopa treatment reduces survival of dopamine cells remaining in the ventral tegmental area of rats with unilateral 6‑OHDA lesions. Rats received L‑dopa and carbidopa in drinking water for 27 weeks after 6‑OHDA lesion surgery, and surviving dopamine cells in the substantia nigra and VTA were quantified by tyrosine hydroxylase immunohistochemistry. Chronic L‑dopa treatment decreased the number of dopamine neurons in the lesioned VTA but did not affect intact substantia nigra or VTA, indicating a suppressive effect of L‑dopa on surviving midbrain dopamine cells after 6‑OHDA exposure.

Abstract

Abstract Ever since the introduction of levo‐3, 4‐dihydroxyphenylalanine (L‐dopa) for the treatment of Parkinson's disease, there has been concern that it might accelerate the degeneration of dopamine neurones. Using rats with a unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the medial forebrain bundle (MFB), we have studied the effect of chronic L ‐dopa treatment on the survival of dopamine cells which remain in the ventral tegmental area (VTA) ipsilateral to a 6‐OHDA lesion. Following lesion surgery, rats were treated with L ‐dopa and carbidopa administered in the drinking water for 27 weeks. At the end of the treatment period, the number of dopamine cells remaining in each of the lesioned and intact substantia nigra (SN) and VTA were assessed, using tyrosine hydroxylase immunohistochemistry. Chronic L ‐dopa treatment resulted in an apparent reduction in the number of dopamine neurones remaining in the VTA ipsilateral to the lesion, whereas it had no effect on the number of dopamine cells remaining in the intact SN and VTA. This finding suggests a possible suppressive effect in vivo of L ‐dopa on dopamine cells in the midbrain of adult animals that have been previously exposed to 6‐OHDA.