|
|
 |
|
Original Article |
|
|
Neuropsychopharmacology (2002) 26 325-339.10.1038/S0893-133X(01)00312-8
Atypical, but Not Typical, Antipsychotic Drugs Increase Cortical Acetylcholine Release without an Effect in the Nucleus Accumbens or Striatum
Junji Ichikawa MD, Ph.D, Jin Dai MD, Ian A O'Laughlin BS, Wiley L Fowler MS and Herbert Y Meltzer MD |
|
|
|
Departments of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
Correspondence: Dr Junji Ichikara, 1601 23rd Avenue South, The First Floor Laboratory R-1117, The Psychiatric Hospital at Vanderbilt, Nashville, TN 37212, USA
|
|
|
|
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.
Keywords: Typical and atypical antipsychotic drugs; Acetylcholine release; Medial prefrontal cortex; Nucleus accumbens; Striatum; Schizophrenia |
|
| |
top  |
|
|
|
|
Send to a friend
Download PDF
Full Text
Next Article
Previous Article
Table of Contents