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Related Experiment Videos

Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated

S O Ogren1, M Goldstein

  • 1Karolinska Institute, Department of Histology and Neurobiology, Stockholm, Sweden.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|November 1, 1994
PubMed
Summary

Dopamine D2 agonists and antagonists differentially affect motor stimulation caused by N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, suggesting distinct NMDA receptor mechanisms.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Neurochemistry

Background:

  • Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists like phencyclidine (PCP) and dizocilpine induce motor stimulation.
  • Dopamine (DA) D2 receptors are implicated in modulating motor activity.

Purpose of the Study:

  • To investigate the influence of dopamine D2 receptor agonists and antagonists on PCP- and dizocilpine-induced locomotion.
  • To explore potential differences in the mechanisms underlying the motor effects of PCP and dizocilpine.

Main Methods:

  • Administration of the DA D2 agonist quinpirole and DA D2 antagonists (haloperidol, raclopride, remoxipride).
  • Assessment of their effects on locomotion induced by equipotent doses of PCP and dizocilpine.
  • Dose-dependent analysis of antagonist efficacy and observation of cataleptogenic effects.

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Main Results:

  • Quinpirole selectively reduced dizocilpine-induced locomotion but not PCP-induced locomotion.
  • DA D2 antagonists dose-dependently blocked motor stimulation by both PCP and dizocilpine.
  • Remoxipride demonstrated potent blockade of both PCP and dizocilpine effects at non-cataleptogenic doses.

Conclusions:

  • PCP and dizocilpine may exert their motor stimulatory effects through distinct NMDA receptor-mediated pathways.
  • Differential interactions with presynaptic NMDA receptors controlling neuronal activity and postsynaptic NMDA receptor subtypes coupled to D2 receptors are suggested.