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

Psychopharmacology (Berl). 1982;77(1):43-52. doi: 10.1007/BF00436098.


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-40s 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 pons-medulla 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apomorphine / pharmacology*
  • Caudate Nucleus / physiology*
  • Conditioning, Operant / drug effects
  • Dopamine / physiology*
  • Drug Tolerance
  • Haloperidol / pharmacology*
  • Macaca mulatta
  • Male
  • Methamphetamine / pharmacology*
  • Receptors, Dopamine / drug effects
  • Synapses / drug effects


  • Receptors, Dopamine
  • Methamphetamine
  • Haloperidol
  • Apomorphine
  • Dopamine