# Dose-Dependent Neuroprotective Effects of Valproate on Motor Function and Striatal D2 Receptor Stability in a 6-OHDA Rat Model of Parkinson’s Disease

## TL;DR

This study shows that high-dose valproic acid protects brain dopamine systems and improves motor function in a rat model of Parkinson’s disease.

## Contribution

The study reveals a dose-dependent neuroprotective effect of valproic acid on dopaminergic terminals and D2 receptor stability in Parkinson’s disease models.

## Key findings

- High-dose valproic acid (400 mg/kg) preserved motor function and dopamine levels in 6-OHDA-lesioned rats.
- Valproic acid at 400 mg/kg normalized striatal D2 receptor expression in the Parkinson’s disease model.
- Low-dose valproic acid (200 mg/kg) had minimal and non-significant effects on motor or biochemical outcomes.

## Abstract

Parkinson’s disease (PD) is characterized by progressive degeneration of nigrostriatal dopaminergic neurons, leading to motor dysfunction and compensatory postsynaptic dopamine receptor alterations. Valproic acid (VPA), a histone deacetylase inhibitor, has shown neuroprotective properties; however, its dose-dependent effects on dopaminergic integrity and dopamine D2 receptor (D2R) regulation remain unclear. Adult male Wistar rats received VPA (200 or 400 mg/kg, p.o.) or vehicle for 20 days prior to unilateral 6-hydroxydopamine (6-OHDA) lesioning. Motor performance was evaluated using the beam balance test, exploratory behavior in the open field, striatal dopamine levels by PLC-electrochemical detection, and D2R protein expression by Western blot. The 6-OHDA lesion induced marked motor deficits, reduced striatal dopamine content, and significantly increased D2R expression. VPA at 200 mg/kg produced only minor, non-significant effects. In contrast, VPA at 400 mg/kg preserved motor performance, attenuated dopamine depletion, and normalized striatal D2R expression. These findings demonstrate a clear dose-dependent neuroprotective effect of VPA and indicate that stabilization of postsynaptic D2R expression accompanies preservation of dopaminergic terminals in the 6-OHDA rat model.