Monoaminergic neuronal changes in orexin deficient mice

Tomohisa Mori, Shinobu Ito, Tomoyuki Kuwaki, Masashi Yanagisawa, Takeshi Sakurai, Toshiko Sawaguchi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Orexin knockout (KO) mice and orexin/ataxin-3 mice (which have a different pathophysiological background in orexin deficiency) exhibit a phenotype that is similar to human narcolepsy. Although the interactions between the monoaminergic and orexinergic systems are not entirely clear, indirect monoamine-receptor agonists (especially psychostimulants) may contribute to the treatment of narcolepsy. The present study was designed to investigate the interaction between brain orexinergic and monoaminergic neurons as measured by the status of monoaminergic systems and monoamine-related behaviors using orexin-deficient mice. Previous studies have shown that a reduction of monoaminergic tone is related to wakefulness. In the present study, locomotor activity in a novel environment and dopamine turnover was significantly decreased in orexin-deficient mice compared to WT mice, which suggests that psychostimulants may be useful for maintaining wakefulness in orexin deficiency. We also examined the effects of orexin deficiency on psychostimulant-induced hyperlocomotion. The hyperlocomotion induced by methamphetamine and methylphenidate was lower, whereas that induced by MDMA was higher in orexin KO mice compared to WT mice. The sensitivities against psychostimulants in orexin/ataxin-3 mice differed from those in orexin KO mice. These results indicate that the effectiveness of each psychostimulant, which is closely related to its monoaminergic function, was influenced by orexin deficiency itself as well as by the different pathophysiological background in orexin deficiency.

Original languageEnglish (US)
Pages (from-to)826-832
Number of pages7
JournalNeuropharmacology
Volume58
Issue number4-5
DOIs
StatePublished - Mar 2010

Fingerprint

Knockout Mice
Narcolepsy
Wakefulness
N-Methyl-3,4-methylenedioxyamphetamine
Methylphenidate
Methamphetamine
Locomotion
Dopamine
Phenotype
Neurons
Brain
Ataxin-3
Therapeutics

Keywords

  • Dopamine
  • Narcolepsy
  • Orexin
  • Orexin knockout mice
  • Orexin/ataxin-3 mice
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Monoaminergic neuronal changes in orexin deficient mice. / Mori, Tomohisa; Ito, Shinobu; Kuwaki, Tomoyuki; Yanagisawa, Masashi; Sakurai, Takeshi; Sawaguchi, Toshiko.

In: Neuropharmacology, Vol. 58, No. 4-5, 03.2010, p. 826-832.

Research output: Contribution to journalArticle

Mori, T, Ito, S, Kuwaki, T, Yanagisawa, M, Sakurai, T & Sawaguchi, T 2010, 'Monoaminergic neuronal changes in orexin deficient mice', Neuropharmacology, vol. 58, no. 4-5, pp. 826-832. https://doi.org/10.1016/j.neuropharm.2009.08.009
Mori, Tomohisa ; Ito, Shinobu ; Kuwaki, Tomoyuki ; Yanagisawa, Masashi ; Sakurai, Takeshi ; Sawaguchi, Toshiko. / Monoaminergic neuronal changes in orexin deficient mice. In: Neuropharmacology. 2010 ; Vol. 58, No. 4-5. pp. 826-832.
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