title: Involvement of orexin-2 receptors in the ventral tegmental area and nucleus accumbens in the antinociception induced by the lateral hypothalamus stimulation in rats.
abstract: Orexin, which is mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Both kinds of orexin-1 (Ox1) and orexin-2 (Ox2) receptors have been found at high density in the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, the quantity of Ox1 receptors in the VTA is more than that in the NAc. Additionally, it seems that the functional interaction between the LH, VTA and NAc implicates pain processing and modulation. In this study, we tried to examine the involvement of Ox2 receptors in the NAc and VTA using tail-flick test as an animal model of acute pain following microinjection of effective dose of carbachol (125nmol/0.5μl saline) into the LH. In this set of experiments, different doses of TCS OX2 29 as an Ox2 receptor antagonist were microinjected into the VTA (1, 7 and 20nmol/0.3μl DMSO) and the NAc (2, 10, 20 and 40nmol/0.5μl DMSO) 5min prior to carbachol administration. Administration of TCS OX2 29 into the VTA and NAc dose-dependently blocked intra-LH carbachol-induced antinociception. However, the inhibitory effect of TCS OX2 29 as an Ox2 receptor antagonist was more potent in the VTA than that in the NAc. It seems that VTA orexinergic receptors are more effective on LH stimulation-induced antinociception and the modulation of pain descending inhibitory system originated from the LH than those of the same receptors in the nucleus accumbens in rats.
authors.affiliation: Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Azhdari-Zarmehri
authors.forename: Zahra
authors.initials: Z
authors.lastname: Reisi
authors.forename: Anoumid
authors.initials: A
authors.lastname: Vaziri
authors.forename: Amir
authors.initials: A
authors.lastname: Haghparast
authors.forename: Pariya
authors.initials: P
authors.lastname: Shaigani
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002404:Catheterization; D006358:Hot Temperature; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism*; D000068797:Orexins; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: C572065:1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; D018712:Analgesics, Non-Narcotic; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D011725:Pyridines; D002217:Carbachol
keywords: Antinociception; Lateral hypothalamus; Nucleus accumbens; Orexin-2 receptor; Rat; Ventral tegmental area