Differential effects of dopaminergic drugs on spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine

Behav Pharmacol. 2017 Dec;28(8):670-680. doi: 10.1097/FBP.0000000000000353.

Abstract

The differential effects of dopaminergic drugs with different pharmacological profiles were investigated with respect to spontaneous motor activity in the common marmoset following pretreatment with a bilateral brain infusion of 6-hydroxydopamine (6-OHDA). Three marmosets received infusions of 6-OHDA (either 30 or 40 μg/side) into the bilateral dopamine-rich area running from the substantia nigra to the striatum. The motor activity of the 6-OHDA marmosets was compared with that of three intact marmosets. Following the administration of apomorphine (0.5 and 1 mg/kg, subcutaneously), the 6-OHDA group showed a tendency toward a brief increase in activity counts, suggesting denervation supersensitivity at the dopamine receptors. After the administration of methamphetamine (1 and 2 mg/kg, subcutaneously), the 6-OHDA group showed a significant decrease in activity counts, indicating limited dopamine release from the degenerated neurons. After the administration of L-3,4-dihydroxyphenylalanine (10 and 20 mg/kg, orally), the 6-OHDA group showed a significant increase in activity counts without hyperexcitation, consistent with the contribution of exogenous L-3,4-dihydroxyphenylalanine toward dopamine synthesis in the degenerated neurons. The present findings indicate that bilateral brain infusion of 6-OHDA in the marmoset may have preclinical utility as a primate model for investigating the behavioral properties of dopaminergic drugs in brains with dopaminergic neural deficits.

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Area Under Curve
  • Callithrix
  • Corpus Striatum / enzymology
  • Corpus Striatum / pathology
  • Disease Models, Animal*
  • Dopamine Agents / pharmacology*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / enzymology
  • Dopaminergic Neurons / pathology
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Levodopa / pharmacology
  • Male
  • Methamphetamine / pharmacology
  • Motor Activity / drug effects*
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / pathology
  • Substantia Nigra / enzymology
  • Substantia Nigra / pathology
  • Tyrosine 3-Monooxygenase

Substances

  • Dopamine Agents
  • Methamphetamine
  • Levodopa
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine