Effects of dopaminergic antagonists on striatal DOPAC concentrations and alpha-methyl-p-tyrosine-induced decline of dopamine following intrastriatal injections of kainic acid
Wuerthele, S.M.; Moore, K.E.
Journal of Pharmacy and Pharmacology 31(3): 180-182
ISSN/ISBN: 0022-3573 PMID: 34696 DOI: 10.1111/j.2042-7158.1979.tb13467.x
The activity of nigrostriatal dopaminergic neurons increases following administration of dopamine antagonists and decreases following dopamine agonists. 3,4-Dihydroxyphenylacetic acid (DOPAC), the major acid metabolite of dopamine, has been used as a biochemical index of dopaminergic nerve activity. DOPAC concentrations may not accurately reflect dopaminergic activity when dopamine terminals are exposed to the toxic effects of kainic acid. Rats treated with kainic acid were injected with either saline, apomorphine HCl, piribedil mesylate, haloperidol, thioridazine HCL, clozapine or sulpiride. Results suggest that under certain circumstances DOPAC is not necessarily equivalent to other indices of dopaminergic nerve activity. When striatal architecture remains intact, DOPAC concentrations parallel dopaminergic nerve activity. However, kainic acid causes neuronal damage near the site of its injection and loss of dopamine. This suggests that the increased DOPAC concentration in kainic acid-treated striata may be due to the inability of damage or degenerating nerve terminals to protect vesicular dopamine stores from intracellular monoamine oxidase.