The effects of thyrotropin-releasing hormone and scopolamine in Alzheimer's disease and normal volunteers

Susan E. Molchan, Alan M. Mellow, James L. Hill, Herbert Weingartner, Rick Martinez, Benedetto Vitiello, Trey Sunderland

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Thyrotropin-releasing hormone (TRH), a neuromodulator and possibly a neurotransmitter in the central nervous system, was shown in a prior study of young normal volunteers to attenuate the memory impairment induced by the anticholinergic drug scopolamine. In the present study, the cognitive, behavioral and physiologic effects of high dose TRH (0.5 mg/kg), both alone and following administration of scopolamine, were examined in 10 Alzheimer's disease (AD) patients (mean age±SD=63.5 years) and 12 older normal volunteers (mean age=64.9±8.8 years). On the day AD subjects received TRH alone, modest but statistically significant improvement from baseline performance was documented on some tests of learning and memory, especially in those with mild dementia severity. In comparing cognitive test performance between the scopolamine alone and scopolamine+TRH conditions, only two test scores were significantly higher in the latter condition. In the group of older volunteers, TRH did not attenuate scopolamine-induced cognitive impairment, contrary to prior findings in a group of younger controls. In fact, older subjects performed worse after receiving scopolamine followed by TRH than after receiving scopolamine alone. In addition, no change from baseline cognitive performance was detected after subjects received TRH alone. These findings raise several questions and speculations on possible age-related changes in the cholinergic system, as well as on the mechanism of the interaction of TRH with the cholinergic system.

Original languageEnglish (US)
Pages (from-to)489-500
Number of pages12
JournalJournal of Psychopharmacology
Issue number4
StatePublished - Jul 1992


  • Alzheimer's disease; ageing
  • memory
  • neuropeptide
  • scopolamine
  • thyrotropin-releasing hormone (TRH)

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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