Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum

Junji Ichikawa*, Jin Dai, Ian A. O'Laughlin, Wiley L. Fowler, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

The role of acetylcholine (ACh) in the action of antipsychotic drugs (APDs) was studied by microdialysis, without AChesterase inhibition, to facilitate the interpretation of any observed drug effects. The atypical APDs, clozapine (2.5-20 mg/kg), olanzapine (10 mg/kg), risperidone (1 mg/kg), and ziprasidone (3 mg/kg) significantly increased ACh release in rat medial prefrontal cortex (mPFC), whereas the typical APDs, haloperidol (0.1-1 mg/kg), S(-)-sulpiride (10-25 mg/g), and thioridazine (5-20 mg/kg) did not. None of seven APDs increased ACh release in the nucleus accumbens or striatum at the doses effective in the mPFC. Thus, atypical and typical APDs may differ in the ability to increase cortical ACh release, a possible factor contributing to cognitive improvement in schizophrenia. After perfusion with neostigmine, an AChesterase inhibitor, clozapine, but not haloperidol, increased ACh release in all three aforementioned brain regions with an enhanced effect in the mPFC, indicating the importance of studying ACh release in the absence of AChesterase inhibition. Clozapine, and perhaps other atypical APDs, alone or in combination with an AChesterase inhibitor, may improve cognition in schizophrenia, and perhaps other cognitive disorders, e.g., early Alzheimer's disease, by enhancing cortical cholinergic transmission.

Original languageEnglish (US)
Pages (from-to)325-339
Number of pages15
JournalNeuropsychopharmacology
Volume26
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Acetylcholine release
  • Medial prefrontal cortex
  • Nucleus accumbens
  • Schizophrenia
  • Striatum
  • Typical and atypical antipsychotic drugs

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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