Effect of clozapine, haloperidol, or M100907 on phencyclidine-activated glutamate efflux in the prefrontal cortex

Barbara W. Adams, Bita Moghaddam

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background: The increase in glutamate efflux in the prefrontal cortex by the psychotomimetic drugs phencyclidine (PCP) and ketamine may produce the dopaminergic and some of the behavioral effects of these drugs. Here, we examined whether antipsychotic drugs influence this increase. Methods: The effect of haloperidol, clozapine or the 5-HT2A antagonist, M100907, on PCP-induced increase in cortical glutamate efflux was examined by microdialysis. Because previous studies had suggested that M100907 attenuates some behavioral effects of PCP, we also examined the effect of M100907 on PCP-induced cortical and accumbal dopamine activation while making concomitant measures of locomotion and stereotypy. Results: Haloperidol, clozapine or M100907 did not significantly block hyperglutamatergic effects of PCP. M100907 was ineffective in inhibiting the dopaminergic and motoric effects of PCP. Conclusions: These results contrast previous findings with glutamatergic drugs, such as AMPA antagonists or group II metabotropic glutamate agonists, that blocked glutamatergic and motoric effects of PCP. Thus, the PCP glutamate activation model lacks predictive validity for conventional antipsychotics; however, this model may be useful for design of novel classes of drugs that target those symptoms of schizophrenia that are not generally treated with monoamine-based antipsychotics.

Original languageEnglish (US)
Pages (from-to)750-757
Number of pages8
JournalBiological Psychiatry
Volume50
Issue number10
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

Fingerprint

Phencyclidine
Clozapine
Haloperidol
Prefrontal Cortex
Glutamic Acid
Pharmaceutical Preparations
Antipsychotic Agents
MDL 100907
Serotonin 5-HT2 Receptor Antagonists
Excitatory Amino Acid Agonists
Dopamine Agents
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Microdialysis
Ketamine
Locomotion
Dopamine
Schizophrenia

Keywords

  • Antipsychotic drugs
  • Ketamine
  • Microdialysis
  • Schizophrenia
  • Serotonin

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Effect of clozapine, haloperidol, or M100907 on phencyclidine-activated glutamate efflux in the prefrontal cortex. / Adams, Barbara W.; Moghaddam, Bita.

In: Biological Psychiatry, Vol. 50, No. 10, 15.11.2001, p. 750-757.

Research output: Contribution to journalArticle

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