title: Orexin A induced antinociception in the ventral tegmental area involves D1 and D2 receptors in the nucleus accumbens.
abstract: Previous studies have shown that there are functional interactions among the lateral hypothalamus (LH), ventral tegmental area (VTA) and the nucleus accumbens (NAc), implicating pain modulation in the central nervous system. It has been shown that the LH-VTA orexinergic projecting neurons play an important role in mediating the suppression of nociception in animal models. However, little is known about the function of intra-VTA orexin receptors and involvement of D1/D2 receptors within the NAc in this antinociception. In the present study, we investigated the effect of direct administration of orexin A into the VTA, and examined the role of intra-accumbal dopamine receptors in tail-flick test as a model of acute nociceptive responses in rats. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the VTA and NAc. The results showed that intra-VTA orexin A (0.055, 0.55, 5.5 and 55ng/0.3μl saline) could induce antinociception in a dose-dependent manner. In two separated supergroups, rats received intra-accumbal infusions of D1 and D2 receptor antagonists, SCH-23390 and sulpiride (0.125, 0.25, 1 and 4μg/rat) prior to intra-VTA orexin A (5.5ng/rat) administration respectively. Antinociceptive responses of drugs are represented as maximal possible effect in 5, 15, 30, 45 and 60min after their administrations. Our findings showed that intra-accumbal SCH-23390 and sulpiride dose-dependently prevented intra-VTA orexin-induced antinociception. Nevertheless, this effect is more potent in animals that received D2 receptor antagonist. It is supposed that orexin A can induce the antinociception through activation of orexinergic receptors which activate the dopaminergic inputs to the NAc in rats.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran; Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Yazdi-Ravandi
authors.affiliation: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Razavi
authors.affiliation: School of Dentistry, International Branch of Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Haghparast
authors.affiliation: Department of Physiology, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Goudarzvand
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran. Electronic address: haghparast@yahoo.com.
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009479:Neuropeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D000068797:Orexins; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D000700:Analgesics; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D013469:Sulpiride
keywords: D1 dopamine receptor; D2 dopamine receptor; Nucleus accumbens; Orexin receptor; Pain; Ventral tegmental area