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Effect of JTP-2942, a Novel TRH Analogue, on Cognitive Function and Learning in Rodents

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Alzheimer’s and Parkinson’s Diseases

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 44))

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Abstract

Thyrotropin-releasing hormone (TRH) is a hypothalamic hormone that releases thyrotropin and prolactin from the anterior pituitary, and is widely distributed throughout the central nervous system (CNS).1–5 It has been shown to have various central actions, such as promoting locomotor activity, increasing body temperature in animals, attenuating pentobarbital induced sleep, and promoting recovery from traumatic loss of consciousness in mice.6–10 TRH also increases cholinergic neuronal activity11–14 and improves memory in amnesia models.15 Currently TRH and its analogues are under clinical investigation for treating spinal cord injury, traumatic brain injury, and dementia including Alzheimer’s disease.16–18 However, TRH has some disadvantages for therapeutic use, including a short duration of action and unsuitability for oral administration. Accordingly, we synthesized a novel TRH analogue, Nα-WS, 2R)-2-methyl-4-oxocyclopentanecarbonyl]-L-histidyl-L-prolineamide monohydrate (JTP2942), with a longer duration of action on the CNS and fewer hormonal effects than TRH.19–21 JTP-2942 has been shown to markedly increase CNS cholinergic neuronal activity22 and improve memory in amnesia models and aged animals.23,24 The callosal-neocortical system is implicated in interhemispheric transfer of the engram and the lateralization of information.25–27 The present study investigated whether JTP-2942 could improve cognitive function and learning in rats subjected to a passive avoidance test after transection of the corpus callosum, and investigated the mechanism of action of this drug using the transcallosal response.

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Authors and Affiliations

  1. Central Pharmaceutical Research Institute, JAPAN TOBACCO INC., Takatsuki, Osaka, 569, Japan

    Fumihiko Yonemori, Hideki Yamada, Atsuhiro Uemura, Satomi Takeuchi, Katsuo Toide & Kunio Iwata

Authors
  1. Fumihiko Yonemori
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  2. Hideki Yamada
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  3. Atsuhiro Uemura
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  4. Satomi Takeuchi
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  5. Katsuo Toide
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  6. Kunio Iwata
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Editor information

Editors and Affiliations

  1. Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA

    Israel Hanin Ph.D.

  2. Jichi Medical School, Tochigi, Japan

    Mitsuo Yoshida M.D.

  3. Israel Institute for Biological Research, Ness-Ziona, Israel

    Abraham Fisher Ph.D.

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© 1995 Springer Science+Business Media New York

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Yonemori, F., Yamada, H., Uemura, A., Takeuchi, S., Toide, K., Iwata, K. (1995). Effect of JTP-2942, a Novel TRH Analogue, on Cognitive Function and Learning in Rodents. In: Hanin, I., Yoshida, M., Fisher, A. (eds) Alzheimer’s and Parkinson’s Diseases. Advances in Behavioral Biology, vol 44. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9145-7_55

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  • DOI: https://doi.org/10.1007/978-1-4757-9145-7_55

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9147-1

  • Online ISBN: 978-1-4757-9145-7

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