Modulation of mPev1 gene expression by anxiolytic drugs in mouse cerebellum

Masashi Akiyama, Tomoko Kirihara, Satomi Takahashi, Yoichi Minami, Yuko Yoshinobu, Takahiro Moriya, Shigenobu Shibata

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

1. The mPer1 and mPer2 genes are putative mouse clock genes that regulate circadian oscillator present in the suprachiasmatic nucleus (SCN) neuron. While they are also expressed in the granular cell layer in the cerebellum, their function is unknown. In a first step to verify the physiological roles of mPev1 and mPer2 genes in the cerebellum, we examined the effects of benzodiazepines on the expression of the mPer1 and mPer2 genes. 2. mPer2 mRNA expression was higher at ZT16 than ZT4 in the mouse cerebellum. 3. High-dose administration of diazepam (10 mg kg-1) or triazolam (1 mg kg-1) reduced mPer1 mRNA level 1 h after treatment in the cerebellum. 4. Reduced expression of mPer1 by diazepam treatment was transient. No difference of mPer1 mRNA level between diazepam (10 mg kg-1)- and vehicle-treated group was observed 6 h after treatment. 5. Administration of high doses of tandospirone (30 mg kg-1), a non-benzodiazepine anxiolytic also reduced mPer1 mRNA expression 1 h after treatment. 6. Administration of high doses of clozapine (5 mg kg-1) or haloperidol (1 mg kg-1) impaired the rota-rod performance without affecting on mPer1 mRNA level. 7. Diazepam and tandospirone inhibited the expression of mPer1 mRNA in the primary cultured cerebellum granule cells. 8. Transient reductions of mPer1 mRNA levels by various benzodiazepines and tandospirone is associated with impairment of coordinated movement, such as rota-rod performance and equilibrium.

Original languageEnglish
Pages (from-to)1616-1622
Number of pages7
JournalBritish Journal of Pharmacology
Volume128
Issue number7
DOIs
Publication statusPublished - 1999

Keywords

  • Anxiolytics
  • Cerebellum
  • Diazepam
  • Rota-rod
  • Tandospirone
  • mPer1

ASJC Scopus subject areas

  • Pharmacology

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