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The Orexin Receptors in the Ventral Tegmental Area Are Involved in the Development of Sensitization to Expression of Morphine-Induced Preference in Rats Publisher Pubmed



Mahmoudi D1 ; Assar N1 ; Mousavi Z2 ; Katebi SN3 ; Azizi P4 ; Haghparast A1
Authors
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Authors Affiliations
  1. 1. Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
  3. 3. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Neuroscience, Integrative Neurobiology of Cholinergic Systems, Pasteur Institute, Paris, France

Source: Behavioural Pharmacology Published:2020


Abstract

Recent studies have shown that orexin neurons in the lateral hypothalamus send a compelling project to the ventral tegmental area (VTA). Besides, orexin-1 (OX1) and orexin-2 (OX2) in the VTA are necessary for the development of morphine-induced place preference. Also, sensitivity to morphine can reinforce the rewarding effects of morphine. The current study aims to determine the role of VTAs orexin receptors in morphine sensitization in rats. In 84 adult male albino Wistar rats, two separate cannulae bilaterally implanted into the VTA. They received intra-VTA infusions of SB334867 (0.1, 1 and 10nM) and TCS OX2 29 (1, 7 and 20nM) as OX1 and OX2 receptor antagonists, respectively, 10min before subcutaneous administration of morphine (5mg/kg) during 3-day sensitization period. After a 5-day drug-free period, the conditioned place preference (CPP) paradigm induced by subthreshold doses of morphine (0.5mg/kg), and CPP scores were measured by EthoVision software. The results revealed that the blockade of both OX1 and OX2 receptors within the VTA reduced the expression of morphine-induced CPP in the sensitized rats. It is plausible that VTAs orexin receptors are involved in the development/acquisition of sensitization to morphine-induced CPP in the rats. © 2020 Wolters Kluwer Health, Inc. All rights reserved
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