Gender differences in the effect of rivastigmine on brain cholinesterase activity and cognitive function in rats

R. H. Wang, C. Bejar, M. Weinstock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

This study compared the effect of rivastigmine on cholinesterase (ChE) activity in different brain regions, heart, skeletal muscle and plasma and on the cognitive impairment induced by scopolamine (0.5 mg/kg) in male and female rats. Rats were injected sc with saline or rivastigmine (0.75-2.5 mg/kg) or physostigmine (0.05 mg/kg) and killed 30-120 min later. Amelioration of scopolamine-induced memory deficits by rivastigmine (0.75 mg/kg) was assessed in the Morris water maze. There were no gender differences in spatial memory or basal ChE activity in the brain or other organs. Rivastigmine (0.75 and 1.5 mg/kg) and physostigmine (0.05mg/kg) caused significantly greater ChE inhibition in females than in males (P<0.01) in the cerebral cortex, hippocampus and striatum, but not in the periphery 30 and 60 min after injection. Rivastigmine was also more effective in antagonising the scopolamine-induced spatial memory impairment in female than in male rats. Ovariectomy did not affect the degree of enzyme inhibition by rivastigmine in any brain area. Orchidectomy completely abolished the difference in enzyme inhibition. It is concluded that a testicular hormone suppresses the effect of rivastigmine, by reducing the amount of drug reaching the brain or its interaction with ChE. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)497-506
Number of pages10
JournalNeuropharmacology
Volume39
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

Keywords

  • Hippocampus
  • Orchidectomy
  • Ovariectomy
  • Physostigmine
  • Skeletal muscle
  • Spatial memory

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