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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Valproic Acid*/pharmacology ; Receptors, Dopamine D2*/metabolism ; Neuroprotective Agents*/pharmacology ; Corpus Striatum*/metabolism ; Corpus Striatum*/drug effects ; Parkinson Disease*/drug therapy ; Parkinson Disease*/metabolism ; Parkinson Disease*/etiology ; Motor Activity*/drug effects; Oxidopamine/toxicity ; Dopamine/metabolism ; Animals ; Male ; Rats ; Disease Models, Animal ; Rats, Wistar ; Dose-Response Relationship, Drug

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.

Keywords: 6-OHDA; HDAC inhibitor; HPLC; Parkinson’s disease; dopamine D2 receptor; neuroprotection; valproic acid

614OI1Z5WI (Valproic Acid)
0 (Receptors, Dopamine D2)
0 (Neuroprotective Agents)
8HW4YBZ748 (Oxidopamine)
VTD58H1Z2X (Dopamine)

Date Created: 20260314 Date Completed: 20260314 Latest Revision: 20260316

20260316

PMC12985796

10.3390/ijms27052320

41828543