Metaphit, a proposed phencyclidine (PCP) antagonist, prevents PCP-induced locomotor behavior through mechanisms unrelated to specific blockade of PCP receptors

Edward D French, Arthur E. Jacobson, Kenner C. Rice

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, has been considered as a potentially specific PCP antagonist. In whole animal studies, however, metaphit has been shown to have either antagonist or PCP-like actions depending upon the animal species used and the experimental variable evaluated. In the present study, the ability of PCP to produce hyperactivity was assessed in rats following pretreatment with intravenous, intraventricular or intracerebral injections of metaphit. Whereas, intravenous and intraventricular metaphit pretreatment failed to alter the locomotor stimulatory effects of PCP, direct injections of metaphit into the nucleus accumbens resulted in a dose-dependent reduction of PCP-induced hyperactivity. This result also was mimicked by intra-accumbens injections of equimolar concentrations of PCP, but not by the local anesthetic procaine. Additionally, intra-accumbens metaphit prevented d-amphetamine-induced hyperactivity and also depleted significantly accumbens dopamine content; effects not seen after intracerebral PCP administration. These results suggest that metaphit produces a functional antagonism of PCP-induced locomotor activity through presynaptic mechanisms unrelated to specific blockade of PCP receptors.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalEuropean Journal of Pharmacology
Volume140
Issue number3
DOIs
StatePublished - Aug 21 1987
Externally publishedYes

Fingerprint

Phencyclidine Receptors
Phencyclidine
Injections
Dextroamphetamine
Procaine
Aptitude
Nucleus Accumbens
Locomotion
Local Anesthetics
metaphit
Dopamine

Keywords

  • Locomotor behavior
  • Metaphit
  • Nucleus accumbens
  • Phenyclidine (PCP)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Metaphit, a proposed phencyclidine (PCP) antagonist, prevents PCP-induced locomotor behavior through mechanisms unrelated to specific blockade of PCP receptors. / French, Edward D; Jacobson, Arthur E.; Rice, Kenner C.

In: European Journal of Pharmacology, Vol. 140, No. 3, 21.08.1987, p. 267-274.

Research output: Contribution to journalArticle

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