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TRH attenuates scopolamine-induced memory impairment in humans

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Abstract

The brain tripeptide thyrotropin-releasing hormone (TRH) has been demonstrated to facilitate cholinergic neurotransmission. To test its interaction with the cholinergic system in humans, high-dose TRH (0.5 mg/kg) or placebo was administered intravenously (IV) to normal controls pretreated with scopolamine (0.5–0.75 mg IV), a centrally active muscarinic antagonist, which has been used to model aspects of the memory impairment of normal aging and of dementia. Compared to placebo, TRH markedly attenuated scopolamine-induced impairment of some measures of memory, most notably on a selective reminding task. This cognitive study is the first in humans to suggest a neuromodulatory effect of a peptide on the cholinergic system, and suggests a facilitatory role for TRH in human memory processes.

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References

  • Bartus RT (1978) Evidence for a direct cholinergic involvement in the scopolamine-induced amnesia in monkeys: evidence of concurrent administration of physostigmine and methylphenidate with scopolamine. Pharmacol Biochem Behav 9:833–836

    Article  PubMed  CAS  Google Scholar 

  • Bassiri RM, Utiger RD (1973) Metabolism and excretion of exogenous thyrotropin releasing hormone in humans. J Clin Invest 52:1616–1619

    Article  PubMed  CAS  Google Scholar 

  • Borowski GD, Garofano CD, Rose LI, Levy RA (1984) Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects. J Clin Endocrinol Metab 58:197–200

    Article  PubMed  CAS  Google Scholar 

  • Breese GR, Cott JM, Cooper BR, Prange AJ, Lipton MA, Plotnikoff NP (1975) Effects of thyrotropin-releasing hormone (TRH) on the actions of pentobarbital and other centrally acting drugs. J Pharmacol Exp Ther 193:11–22

    PubMed  CAS  Google Scholar 

  • Buschke H (1973) Selective reminding for analysis of memory and learning. J Verb Learn Verb Behav 12:543–550

    Article  Google Scholar 

  • Caine ED, Weingartner H, Ludlow DL, Cudahy EA, Wehry S (1981) Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 74:74–80

    Article  PubMed  CAS  Google Scholar 

  • Drachman DA (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27:783–790

    PubMed  CAS  Google Scholar 

  • Dunne MP, Hartley LR (1985) The effects of scopolamine upon verbal memory: evidence for an attentional hypothesis. Acta Psychol 58:205–217

    Article  CAS  Google Scholar 

  • Hasher L, Zacks RT (1979) Automatic and effortful processes in memory. J Exp Psychol [Gen] 108:356–388

    Article  Google Scholar 

  • Horita A, Carino MA, Lai H (1986) Pharmacology of thyrotropin-releasing hormone. Annu Rev Pharmacol Toxicol 26:311–332

    Article  PubMed  CAS  Google Scholar 

  • Horita A, Carino MA, Lai H (1987) Preliminary studies of the effects of a TRH analog, MK-771, in an animal model of Alzheimer's disease. Proc West Pharmacol Soc 30:57–58

    PubMed  CAS  Google Scholar 

  • Jackson IMD (1982) Thyrotropin-releasing hormone. New Engl J Med 306:145–155

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Horita A (1980) Thyrotropin-releasing hormone: neurogenesis of actions in the pentobarbital narcotized rat. J Pharmacol Exp Ther 212:203–210

    PubMed  CAS  Google Scholar 

  • van Kammen DP, Murphy DL (1975) Attenuation of the euphoriant and activating effects ofd- andl-amphetamine by lithium carbonate treatment. Psychopharmacologia 44:215–224

    Article  PubMed  Google Scholar 

  • Lamour Y, Dutar P, Jobert A (1985) Effects of TRH, cyclo-(His-Pro) and (3-Me-His)TRH on identified septohippocampal neurons in the rat. Brain Res 331:343–347

    Article  PubMed  CAS  Google Scholar 

  • Manaker S, Eichen A, Winokur A, Rhodes CH, Rainbow TC (1986) Autographic localization of thyrotropin releasing hormone receptors in human brain. Neurology 36:641–646

    PubMed  CAS  Google Scholar 

  • Mellow AM, Sunderland T, Cohen RM, Lawlor BA, Hill JL, Newhouse PA, Cohen MR, Murphy DL (1989) Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease. Psychopharmacology 98:403–407

    Article  PubMed  CAS  Google Scholar 

  • Metcalf G (1982) Regulatory peptides as a source of new drugs: the clinical prospects for analogues of TRH which are resistant to metabolic degradation. Brain Res Rev 4:389–408

    Article  CAS  Google Scholar 

  • Mewaldt SP, Ghoneim MM (1979) The effects and interactions of scopolamine, physostigmine and methamphetamine on human memory. Pharmacol Biochem Behav 10:205–210

    Article  PubMed  CAS  Google Scholar 

  • Mitsumoto H, Salgado ED, Negroski D, Hanson MR, Salanga VD, Wilber JF, Wilbourn AJ, Breur AC, Leatherman J (1986) Amyotrophic lateral sclerosis: effects of acute intravenous and chronic subcutaneous administration of thyrotropin-releasing hormone in controlled trials. Neurology 36:152–159

    PubMed  CAS  Google Scholar 

  • Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10:799–812

    Article  Google Scholar 

  • Perry EK, Tomlinson BE, Blessed G, Bergman K, Bigson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2:1457–1459

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer E (1975) A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 23:433–441

    PubMed  CAS  Google Scholar 

  • Safer DJ, Allen RP (1971) The central effects of scopolamine in man. Biol Psychiatry 3:347–355

    PubMed  CAS  Google Scholar 

  • Schmidt DE (1977) Effects of thyrotropin releasing hormone (TRH) on pentobarbital-induced decrease in cholinergic neuronal activity. Psychopharmacol Commun 1:469–473

    CAS  Google Scholar 

  • Sitaram N, Weingartner H, Gillin JC (1978) Human serial learning: enhancement with arecholine and choline impairment with scopolamine. Science 201:274–276

    Article  PubMed  CAS  Google Scholar 

  • Snyder PJ, Utiger RD (1972) Response to thyrotropin releasing hormone (TRH) in normal man. J Clin Endocrinol Metab 34:380–385

    Article  PubMed  CAS  Google Scholar 

  • Sunderland T, Tariot PN, Weingartner H, Murphy DL, Newhouse PA, Mueller EA, Cohen RM (1986) Pharmacologic modelling of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 10:599–610

    Article  PubMed  CAS  Google Scholar 

  • Sunderland T, Tariot PN, Cohen RM, Weingartner H, Muekker EA, Murphy DL (1987) Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls. Arch Gen Psychiatry 44:418–426

    PubMed  CAS  Google Scholar 

  • Weingartner H, Grafman J, Boutelle W, Kaye W, Martin PR (1983) Forms of memory failure. Science 221:380–382

    Article  PubMed  CAS  Google Scholar 

  • Weingartner H, Burns D, Diebel R, LeWitt PA (1984) Cognitive impairments in Parkinson's disease: distinguishing between effort-demanding and automatic cognitive processes. Psychiatry Res 11:223–235

    Article  PubMed  CAS  Google Scholar 

  • Winokur A, Beckman AL (1978) Effects of thyrotropin-releasing hormone, norepinephrine and acetylcholine on the activity of neurons in the hypothalamus, septum and cerebral cortex of the rat. Brain Res 150:205–209

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki N, Nagaoka N, Nagawa Y (1986) Effect of thyrotropin-releasing hormone and its analog DN-1417 on scopolamine-induced impairment of short-term memory in rats. Jpn J Psychopharmacol 6:359–366

    CAS  Google Scholar 

  • Yarbrough GG (1979) On the neuropharmacology of thyrotropin releasing hormone (TRH). Prog Neurobiol 12:291–312

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Unit on Geriatric Psychopharmacology, Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, 9000 Rockville Pike, 20892, Bethesda, MD, USA

    Susan E. Molchan, Brian A. Lawlor & Trey Sunderland

  2. Department of Psychiatry, University of Michigan Medical Center, 1103 East Huron, 48104, Ann Arbor, MI, USA

    Alan M. Mellow

  3. Department of Psychology, George Washington University, 2125 G Street, N.W., 20036, Washington, DC, USA

    Herbert J. Weingartner

  4. Section on Clinical Brain Imaging, Laboratory of Cerebral Metabolism, National Institute of Mental Health, 9000 Rockville Pike, 20892, Bethesda, MD, USA

    Robert M. Cohen

  5. Ensor Research Laboratory, William S. Hall Psychiatric Institute, University of South Carolina School of Medicine, P.O. Box 202, 29202, Columbia, SC, USA

    Martin R. Cohen

Authors
  1. Susan E. Molchan
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  2. Alan M. Mellow
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  3. Brian A. Lawlor
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  4. Herbert J. Weingartner
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  5. Robert M. Cohen
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  6. Martin R. Cohen
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  7. Trey Sunderland
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Molchan, S.E., Mellow, A.M., Lawlor, B.A. et al. TRH attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 100, 84–89 (1990). https://doi.org/10.1007/BF02245795

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  • DOI: https://doi.org/10.1007/BF02245795

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