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  • Title: Tolerance develops to the haloperidol-induced increase in the efflux of dopamine metabolites from the brains of unanesthetized, freely-moving rats.
    Author: Nielsen JA, Duda NJ, Moore KE.
    Journal: Life Sci; 1982 Oct 04; 31(14):1495-1500. PubMed ID: 6183554.
    Abstract:
    The lateral cerebral ventricles of freely moving rats were perfused by means of chronically implanted push-pull cannulae every second day for 2 weeks. Perfusates were analyzed for metabolites of dopamine [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] and of 5-hydroxytryptamine [5-hydroxyindoleacetic acid (5HIAA)] using high performance liquid chromatography and an amperometric detector. Rats received daily subcutaneous injections of haloperidol (1 mg/kg) or its vehicle. After the first injection of haloperidol the concentrations of DOPAC and HVA were markedly increased while that of 5HIAA was unchanged. Complete tolerance developed to the haloperidol-induced increased efflux of dopamine metabolites by day 9, although a higher dose of haloperidol (2 mgf/kg) on day 15 was still capable of eliciting a modest increase in the efflux of DOPAC and HVA.
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