Relationship between cholinergic dysfunction and discrimination learning disabilities in Wistar rats following chronic cerebral hypoperfusion

Ken Ichi Tanaka, Norio Ogawa, Masato Asanuma, Yoichi Kondo, Masahiko Nomura

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

The effects of chronic hypoperfusion of cerebral blood flow (CBF) on central cholinergic indices and intellectual functions were investigated in rats. Male Wistar rats, aged 9 weeks, were anesthetized with pentobarbital, and the bilateral common carotid arteries were permanently ligated. Cortical CBF in the hypoperfused rats was markedly decreased at 6 weeks after the operation. In the hypoperfused group, cholinergic indices were changed to consist two phases after the operation, before (acute) and after (chronic) 6 weeks after the operation. At 6 weeks, choline acetyltransferase activity was restored to the sham-operated level compared with the changes in the frontal cortex and thalamus + midbrain at 3 weeks. On the other hand, the maximum number of muscarinic acetylcholine receptors was reduced in the frontal cortex, hippocampus and striatum at 6 weeks and thereafter remained at this low level. In discrimination learning task, the percentage of correct responses in the hypoperfused rats was generally reduced in contrast with that of the sham-operated rats, although the number of total responses were not changed. As a consequence, cholinergic dysfunctions correlate with discrimination learning disabilities in the hypoperfused rats. These findings suggest that the hypoperfused rat may be useful for the cerebrovascular type dementia model to clarify pathophysiology.

Original languageEnglish
Pages (from-to)55-65
Number of pages11
JournalBrain Research
Volume729
Issue number1
DOIs
Publication statusPublished - Aug 5 1996

Keywords

  • Cerebrovascular type dementia
  • Chronic hypoperfusion
  • Discrimination learning
  • Incomplete ischemia
  • Ligation of bilateral common carotid artery
  • Muscarinic acetylcholine receptor
  • Rarefaction
  • Wistar rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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