Physostigmine reversal of scopolamine-induced hypofrontality

I. Prohovnik, S. E. Arnold, G. Smith, L. R. Lucas

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The muscarinic receptor antagonist scopolamine produces a transient memory deficit in healthy humans. This deficit has been offered as a model of the cholinergic deficit of Alzheimer's disease (AD). However, we have previously shown that scopolamine produces a deficit of cortical perfusion maximal in the frontal lobe, dissimilar to the parietal cortex deficit characteristic of AD. The current experiment was aimed at replicating and extending this observation by critically testing the central cholinergic origin of both cognitive and perfusion deficits. Nine healthy subjects participated in regional cerebral blood flow (rCBF) measurements at baseline, after scopolamine (7.2 μg/kg i.v.), and after both physostigmine (22 μg/kg i.v.) and neostigmine (7 or 11 μg/kg i.v.). rCBF was quantified by the xenon 133 inhalation method. As expected, scopolamine reduced cortical perfusion, mainly in the frontal cortex, and produced a memory deficit. Physostigmine, but not neostigmine, reversed all three variables partiallyor completely. These results support the hypothesis that all three consequences of scopolamine, namely, reduction of mean flow, frontal deficit, and memory impairment, are cholinergically mediated. Furthermore, because neostigmine poorly crosses the blood-brain barrier, these findings confirm that the effect is centrally mediated and cannot be explained by peripheral effects. However, they also confirm the frontal cortex locus of action for both scopolamine and its reversal by physostigmine and therefore suggest a major dissimilarity to the characteristic rCBF appearance of AD. This study extends our previous preliminary findings with tacrine and strengthens the suggestion that only nicotinic receptors are associated with the characteristic parietal deficit of AD.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number2
StatePublished - Feb 1997
Externally publishedYes


  • Acetyl-cholinesterase inhibitors
  • Alzheimer's disease
  • Cerebral metabolism
  • Cerebral perfusion
  • Neostigmine
  • Physostigmine
  • Scopolamine
  • Tacrine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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