Anaesthesia abolishes the effect of valproate on extracellular 5‐HIAA, DOPAC and ascorbate as measured in rat striatum by differential pulse voltammetry

1 The effect of sodium valproate (VPA, 400 mg kg−1, i.p.) on extracellular ascorbate, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was examined by differential pulse voltammetry in anaesthetized and freely-moving rats. 2 In rats anaesthetized with chloral hydrate (400 mg kg−1, i.p.), pentobarbitone (50 mg kg−1, i.p.) or phenobarbitone (60 mg kg−1, i.p.), VPA produced no significant changes in peak 1 (extracellular ascorbate) or peak 2 (extracellular DOPAC), but produced a slight but statistically significant reduction in the height of peak 3 (extracellular 5-HIAA). 3 In contrast, in freely-moving rats the same dose of VPA greatly reduced extracellular ascorbate and DOPAC concentrations, and increased that of 5-HIAA. 4 These results suggest that VPA may reduce the release or turnover of dopamine, and increase that of 5-hydroxytryptamine in conscious rats. Our data also suggest that caution may be required in the interpretation of the effects of VPA in anaesthetized animals, as the results obtained may not always reflect the situation in the absence of anaesthesia.