Neurochemical and behavioral effects of acute and chronic treatment with apomorphine in rats

J. K. Rowlett, B. A. Mattingly, M. T. Bardo

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35 Scopus citations

Abstract

In three experiments, rats were injected once daily with 5.0 mg/kg apomorphine or vehicle and tested for locomotor activity for 10-14 days. In each experiment, apomorphine produced behavioral sensitization, characterized by a progressively greater increase in locomotor activity with each succeeding injection. On day 11 of testing, in an experiment designed to assess the synthesis of dopamine (DA), rats were injected with 5.0 mg/kg apomorphine or vehicle, followed by 100 mg/kg NSD-1015, an inhibitor of the enzyme l-aromatic amino acid decarboxylase. After administration of NSD-1015, concentrations of dihydroxyphenylalanine (DOPA) were determined in striatal and mesolimbic tissues by high performance liquid chromatography (HPLC) with electrochemical detection. The results revealed a significant decrease in accumulation of DOPA in both striatal and mesolimbic tissue after acute treatment with apomorphine. More important, chronic treatment with apomorphine produced a significant increase in accumulation of DOPA in both areas. In subsequent experiments, rats on day 14 of testing were sacrificed for determination of levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) or specific binding of [3H]spiperone in the striatum and mesolimbic region. Although levels of DOPAC were significantly reduced in the regions of the brain after an acute injection of apomorphine, chronic treatment with apomorphine did not significantly affect levels of DA, DOPAC or specific binding of [3H]spiperone. These findings suggest that the development of behavioral sensitization to apomorphine may be related to an alteration in the synthesis of DA.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalNeuropharmacology
Volume30
Issue number2
DOIs
StatePublished - Feb 1991

Bibliographical note

Funding Information:
Acknowledgements--We gratefully acknowledge the technical assistance of Rosalyn Ennis and Jamison Graft in collecting some of these data. The authors would also like to thank R. C. Pierce for helpful comments on an earlier version of this manuscript. This research was supported by a Kentucky EPSCoR grant and Morehead State University faculty grants to B.A.M.

Keywords

  • apomorphine
  • behavioral sensitization
  • dopamine
  • mesolimbic system
  • striatum

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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