PT  - JOURNAL ARTICLE
AU  - Minoru Narita
AU  - Yasuyuki Nagumo
AU  - Seiko Hashimoto
AU  - Michiko Narita
AU  - Junaidi Khotib
AU  - Mayumi Miyatake
AU  - Takeshi Sakurai
AU  - Masashi Yanagisawa
AU  - Tomoya Nakamachi
AU  - Seiji Shioda
AU  - Tsutomu Suzuki
TI  - Direct Involvement of Orexinergic Systems in the Activation of the Mesolimbic Dopamine Pathway and Related Behaviors Induced by Morphine
AID  - 10.1523/JNEUROSCI.2761-05.2006
DP  - 2006 Jan 11
TA  - The Journal of Neuroscience
PG  - 398--405
VI  - 26
IP  - 2
4099  - http://www.jneurosci.org/content/26/2/398.short
4100  - http://www.jneurosci.org/content/26/2/398.full
SO  - J. Neurosci.2006 Jan 11; 26
AB  - 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.