Altered sensitivity to d-methylamphetamine, apomorphine, and haloperidol in rhesus monkeys depleted of caudate dopamine by repeated administration of d-methylamphetamine

K. T. Finnegan, G. Ricaurte, L. S. Seiden, C. R. Schuster

Research output: Contribution to journalArticlepeer-review

Abstract

The long-term neurochemical and behavioral effects of repeated d-methylamphetamine (d-MA) administration were investigated using four male rhesus monkeys trained to lever-press for food on a DRL-40 s schedule of reinforcement. Dose-response curves for d-MA (0.0625-2.0 mg/kg), apomorphine (0.025-0.4 mg/kg), and haloperidol (0.005-0.04 mg/kg) on responding showed that repeated d-MA administration (0.5-16.0 mg/kg/day) decreased sensitivity to d-MA and to apomorphine but increased sensitivity to haloperidol. At 3-6 months after the last injection of d-MA, a 48.1% decrease in caudate dopamine (DA) was observed, with the frontal cortex, midbrain, and ponsmedulla showing no significant change. A trend toward increasing concentrations of norepinephrine was noted in the same brain areas, but only in the frontal cortex did this change reach significance. Specific binding of 3H-spiroperidol to caudate membrane preparations was not changed, while the Vmax of the caudate DA re-uptake process declined 32%, with no change in Km. These results suggest that exposure of DA neurons in the caudate nucleus to high concentrations of d-MA can lead to nerve terminal degeneration.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalPsychopharmacology
Volume77
Issue number1
DOIs
StatePublished - May 1 1982
Externally publishedYes

Keywords

  • Amphetamines
  • DRL Schedule
  • Dopamine
  • Neurotoxicity
  • Tolerance
  • d-Methylamphetamine

ASJC Scopus subject areas

  • Pharmacology

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