Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats

Eur Neuropsychopharmacol. 2007 Sep;17(9):616-26. doi: 10.1016/j.euroneuro.2007.02.011. Epub 2007 Apr 30.

Abstract

This study examined the effects of subsequent, subchronic, treatment with choline uptake enhancer MKC-231 on the behavioral and cellular deficits induced by repeated PCP exposure in rats. Prior subchronic PCP exposure resulted in increased locomotion following an acute PCP or cocaine challenge, but resulted in decreased locomotor activity in response to a carbachol-challenge. MKC-231 significantly antagonized the alterations in the locomotor responses to cocaine and carbachol, but not to PCP. In the novel object recognition test, repeated PCP exposure caused cognitive deficits in rats, and the PCP-induced cognitive deficits were antagonized by MKC-231. In contrast, no effects of PCP exposure were shown in the repeated passive avoidance test. Furthermore, repeated PCP exposure decreased a number of choline acetyltransferase (ChAT)-positive cells in the medial septum and increased dynorphin A expression in the ventral striatum. Moreover, MKC-231 significantly antagonized the changes in septal ChAT-positive cells, but not the changes in ventrostriatal dynorphin A expression. These results suggest that MKC-231 could be a therapeutic drug for the treatment of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Drug Administration Schedule
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Gene Expression Regulation / drug effects
  • Male
  • Mental Disorders / chemically induced
  • Mental Disorders / drug therapy*
  • Mental Disorders / pathology
  • Motor Activity / drug effects
  • Neurons / drug effects*
  • Neurons / pathology
  • Phencyclidine*
  • Quinolines / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Septum of Brain / pathology*
  • Time Factors

Substances

  • Quinolines
  • Choline O-Acetyltransferase
  • Phencyclidine
  • Acetylcholine
  • MKC 231