論文

査読有り
2016年

Learning and memory deficits in male adult mice treated with a benzodiazepine sleep-inducing drug during the juvenile period

Frontiers in Neuroscience
  • Yusuke Furukawa
  • ,
  • Kentaro Tanemura
  • ,
  • Katsuhide Igarashi
  • ,
  • Maky Ideta-Otsuka
  • ,
  • Ken-Ichi Aisaki
  • ,
  • Satoshi Kitajima
  • ,
  • Masanobu Kitagawa
  • ,
  • Jun Kanno

10
339
開始ページ
339
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3389/fnins.2016.00339
出版者・発行元
Frontiers Media S.A.

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R) mediated signaling (GABA-R signal) during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ) or the non-benzodiazepine drug zolpidem (ZP). We detected learning and memory deficits in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs), which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible learning and memory deficits in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause learning and memory deficits.

リンク情報
DOI
https://doi.org/10.3389/fnins.2016.00339
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27489535

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