Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine

Minoru Narita, Yasuyuki Nagumo, Seiko Hashimoto, Michiko Narita, Junaidi Khotib, Mayumi Miyatake, Takeshi Sakurai, Masashi Yanagisawa, Tomoya Nakamachi, Seiji Shioda, Tsutomu Suzuki

Research output: Contribution to journalArticlepeer-review

392 Scopus citations

Abstract

In this study, we investigated the role of orexinergic systems in dopamine-related behaviors induced by the μ-opioid receptor agonist morphine in rodents. Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed in the mouse ventral tegmental area (VTA). The levels of dopamine and its major metabolites in the nucleus accumbens were markedly increased by the microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine-induced place preference and hyperlocomotion observed in wild-type mice were abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place preference in rats. Furthermore, the increased level of dialysate dopamine produced by morphine in the mouse brain was significantly decreased by deletion of the prepro-orexin gene. These findings provide new evidence that orexin-containing neurons in the VTA are directly implicated in the rewarding effect and hyperlocomotion induced by morphine through activation of the mesolimbic dopamine pathway in rodents.

Original languageEnglish (US)
Pages (from-to)398-405
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number2
DOIs
StatePublished - Jan 11 2006

Keywords

  • Addiction
  • Dependence
  • Morphine
  • Opioid
  • Orexin
  • Reward

ASJC Scopus subject areas

  • Neuroscience(all)

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