Abstract
The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a “DA D2 autoreceptor selective” dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on “regulatory” NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ögren, S., Goldstein, M. Phencyclidine- and Dizocilpine-Induced Hyperlocomotion Are Differentially Mediated. Neuropsychopharmacol 11, 167–177 (1994). https://doi.org/10.1038/sj.npp.1380103
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.npp.1380103
Keywords
This article is cited by
-
The unconventional activation of the muscarinic acetylcholine receptor M4R by diverse ligands
Nature Communications (2022)
-
Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex
Molecular Psychiatry (2016)
-
Chronic Phencyclidine Induces Inflammatory Responses and Activates GSK3β in Mice
Neurochemical Research (2014)
-
1-Methyl-1,2,3,4-tetrahydroisoquinoline Antagonizes a Rise in Brain Dopamine Metabolism, Glutamate Release in Frontal Cortex and Locomotor Hyperactivity Produced by MK-801 but not the Disruptions of Prepulse Inhibition, and Impairment of Working Memory in Rat
Neurotoxicity Research (2009)
-
The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss
Neuropsychopharmacology (2008)