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Psychopharmacology

, Volume 104, Issue 2, pp 194–200 | Cite as

Influence of acute and chronic haloperidol treatment on dopamine metabolism in the rat caudate-putamen, prefrontal cortex and amygdala

  • Eva C. Essig
  • Ian C. Kilpatrick
Original Investigations

Abstract

The present study investigated the actions of single and repeated injections of the classical anti-psychotic drug, haloperidol (1 mg · kg−1 IP), on dopamine (DA) metabolism in three distinct rat brain regions, namely the prefrontal cortex, amygdala and caudateputamen (CP), using a high-performance liquid chromatographic assay. Acute administration of the drug caused significant elevations in concentrations of two major DA metabolites in all three areas studied. Less marked acute increases were seen in the CP following 10 days of repeated haloperidol treatment. However, in both the prefrontal cortex and the amygdala, the development of such “tolerance” was somewhat delayed in comparison, occurring only after a 22-day treatment schedule. The amygdala displayed the greatest degree of neurochemical tolerance, returning to control values by day 22 of chronic treatment. When allowance was made for the withdrawal effects of antipsychotic drug administration, a genuine tolerance phenomenon was observed in all three areas examined. These data suggest that if neurochemical tolerance is a prerequisite for functional DA receptor blockade and hence therapeutic efficacy, then both the prefrontal cortex and amygdala should be considered as potential therapeutic targets of haloperidol and perhaps antipsychotic drugs in general.

Key words

Dopamine Metabolism Amygdala Prefrontal cortex Caudate-putamen Haloperidol Tolerance Neuroleptic (chronic) 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Eva C. Essig
  • Ian C. Kilpatrick
    • 1
  1. 1.Department of Pharmacology, School of Medical SciencesUniversity WalkBristolUK

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