Differential cholinergic regulation in Alzheimer's patients compared to controls following chronic blockade with scopolamine: a SPECT study

T. Sunderland, G. Esposito, S. E. Molchan, R. Coppola, D. W. Jones, J. Gorey, John Timothy Little, M. Bahro, D. R. Weinberger

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of low-dose chronic scopolamine on measures of cerebral perfusion and muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and eight elderly controls. Single photon emission computed tomography (SPECT) scans using technetium-labelled hexamethypropylene amine oxide (99mTc-HMPAO) to measure cerebral perfusion before and after chronic scopolamine revealed a significant 12% increase in the normal controls (P<0.01) while the AD subjects showed no significant change. In contrast, the controls showed decreased muscarinic binding as evidenced by123I-quinuclidinyl-4-iodobenzilate (123I-QNB) labelling after chronic drug (-10%, P<0.01) whereas the AD subjects showed increased123I-QNB labelling (+8%, P<0.05). The difference between AD and control subjects was even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing to a double dissociation in the SPECT results. These data cannot be explained by group differences in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalPsychopharmacology
Volume121
Issue number2
DOIs
StatePublished - Sep 1 1995
Externally publishedYes

Keywords

  • Alzheimer's disease
  • HMPAO
  • I-QNB
  • SPECT
  • Scopolamine
  • cholinergic

ASJC Scopus subject areas

  • Pharmacology

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