Augmentation of locomotor activity by chronic phencyclidine is associated with an increase in striatal NMDA receptor function and an upregulation of the NR1 receptor subunit

Taleen Hanania, Gilbert R. Hillman, Kenneth M. Johnson

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Phencyclidine (PCP) is a drug of abuse that produces schizophrenia-like symptoms in humans and increases locomotor activity and stereotypic behavior in rodents. PCP-induced alteration in rat locomotor activity is thought to be mediated by an inhibition of N-methyl-D-aspartate (NMDA) receptors in the striatum and other brain regions. In this study, rats treated chronically with PCP (20 mg/kg once per day for 5 days) showed a marked increase in locomotor activity following a PCP challenge (3.2 mg/kg) administered after either 3 or 8 days of withdrawal. In biochemical assays, the release of striatal [14C]GABA by NMDA was enhanced by about 77% by chronic PCP treatment, whereas [3H]ACh release was increased by about 31% in tissue from PCP-treated rats. Even though binding experiments with 1-[1-(2- thiehyl)cyclohexyl]piperidyl-3,4 3H(N) ([3H]TCP) showed no alteration in the Kd or Bmax in whole striatum, quantitative immunocytochemical experiments found an upregulation in the NR1 subunit in the cell bodies and neuropil of cortical and striatal regions of the forebrain following chronic PCP treatment. An increase in the size of NR1-immunoreactive cells in the forebrain was also observed following chronic PCP treatment. Together, these data may help in understanding the mechanisms underlying the adaptive response to chronic reduction in glutamatergic NMDA transmission that has been postulated to be involved in the etiology of schizophrenia.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalSynapse
Volume31
Issue number3
DOIs
StatePublished - Mar 1 1999

Fingerprint

Corpus Striatum
Phencyclidine
Locomotion
N-Methyl-D-Aspartate Receptors
Up-Regulation
N-Methylaspartate
Prosencephalon
Schizophrenia
Neuropil
Street Drugs
gamma-Aminobutyric Acid
Rodentia
Brain

Keywords

  • Acetylcholine
  • Frontal cortex
  • GABA
  • Olfactory cortex
  • Release
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Augmentation of locomotor activity by chronic phencyclidine is associated with an increase in striatal NMDA receptor function and an upregulation of the NR1 receptor subunit. / Hanania, Taleen; Hillman, Gilbert R.; Johnson, Kenneth M.

In: Synapse, Vol. 31, No. 3, 01.03.1999, p. 229-239.

Research output: Contribution to journalArticle

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