, Volume 120, Issue 3, pp 280–288 | Cite as

Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans

  • J. T. Little
  • A. Broocks
  • A. Martin
  • J. L. Hill
  • L. E. Tune
  • C. Mack
  • M. Cantillon
  • S. Molchan
  • D. L. Murphy
  • T. Sunderland
Original Investigation


Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonistm-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine + ondansetron, and scopolamine + m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.

Key words

Scopolamine Ondansetron m-Chlorophenylpiperazine Cognitive pharmacologic modeling Geriatrics 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • J. T. Little
    • 1
  • A. Broocks
    • 2
  • A. Martin
    • 1
  • J. L. Hill
    • 1
  • L. E. Tune
    • 3
  • C. Mack
    • 1
  • M. Cantillon
    • 1
  • S. Molchan
    • 1
  • D. L. Murphy
    • 1
  • T. Sunderland
    • 1
  1. 1.Section on Psychobiology, Biological Psychiatry Branch, and Sections On Geriatric Psychiatry, Neuropharmacology, and Unit On Cognitive Studies, Laboratory of Clinical ScienceNational Institute of Mental HealthBethesdaUSA
  2. 2.Department of PsychiatryGoettingen UniversityGoettingenGermany
  3. 3.Department of PsychiatryEmory UniversityAtlantaUSA

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