title: Dexmedetomidine induces conditioned place preference in rats: Involvement of opioid receptors.
abstract: Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered "biased" as the animals preferred the grid side to the mesh side. Male Wistar albino rats weighing 250-300 g were divided into several groups, including control (saline), morphine (10mg/kg), DEX (2.5-20 μg/kg), naloxone alone (0.5mg/kg) and a combination (0.5mg/kg naloxone plus 20 μg/kg DEX) (n=7-8 for each group). The CPP effects of morphine, DEX, saline and the combination were evaluated. All the drug and saline administrations except naloxone were performed by intraperitoneal (ip) injections. Naloxone was injected subcutaneously (sc) when given alone or in combination with DEX. Morphine (10mg/kg) and DEX (5-20 μg/kg) produced CPP that were statistically significant relative to saline-injected rats. DEX-induced CPP was significantly reversed by pretreatment with naloxone, an opioid antagonist. Naloxone alone treatment did not cause any significant effect on CPP. Our results suggest that DEX produces CPP effects similar to morphine in rats and that opioidergic mechanism may be responsible for DEX-induced CPP. Thus, DEX might have the potential to be addictive, and this possibility should be considered during clinical application of this drug.
authors.affiliation: Istanbul University, Institute of Health Science,Cerrahpasa Medical Faculty, Department of Medical Pharmacology, Istanbul, Turkey.
authors.forename: Tuğçe
authors.initials: T
authors.lastname: Uskur
authors.affiliation: Istanbul University, Institute of Health Science,Cerrahpasa Medical Faculty, Department of Medical Pharmacology, Istanbul, Turkey.
authors.forename: M Aydın
authors.initials: MA
authors.lastname: Barlas
authors.affiliation: Istanbul University, Institute of Health Science,Cerrahpasa Medical Faculty, Department of Medical Pharmacology, Istanbul, Turkey.
authors.forename: A Gökhan
authors.initials: AG
authors.lastname: Akkan
authors.affiliation: Istanbul University, Institute of Health Science,Cerrahpasa Medical Faculty, Department of Medical Pharmacology, Istanbul, Turkey.
authors.forename: Andleeb
authors.initials: A
authors.lastname: Shahzadi
authors.affiliation: Uskudar University, Neuropsychopharmacology Application and Research Center (NPARC), Altunizade Mah, Haluk Turksoy Sok, No: 14 34662 Üsküdar, Istanbul, Turkey. Electronic address: uzbayt@yahoo.com.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Uzbay
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D020927:Dexmedetomidine
keywords: Addiction; Conditioned place preference; Dexmedetomidine; Morphine; Opioids; Rat(s)