Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system.
We demonstrated involvement of the ventral tegmental area (VTA) dopaminergic system in orexin-induced hyperlocomotion and stereotypy in rats. In double-label immunohistochemical study of rat brain, we found that tyrosine hydroxylase (TH)-immunoreactive cells in the VTA received innervation from orexin immunoreactive-fibers. Orexin-A induced an increase in [Ca(2+)](i) in isolated A10 dopamine neurons in a dose-dependent manner. In behavioral studies, we found that orexin-A induced hyperlocomotion, stereotypy and grooming behavior when administered centrally in rats, and these effects were abolished by dopamine D(2) (haloperidol and sulpiride) or D(1) (SCH23390) antagonists. These results suggest that the orexin-induced hyperlocomotion, stereotypy and grooming behavior are mediated by the dopaminergic system and this pathway might be involved in orexin-induced emotional responses.
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
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Nakamura
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Uramura
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Nambu
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Yada
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Goto
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Yanagisawa
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Sakurai
D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D002352:Carrier Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D009411:Nerve Endings / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001552:Benzazepines; D002352:Carrier Proteins; D018492:Dopamine Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D013469:Sulpiride; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine