title: The adenosinergic system is involved in sensitization to morphine withdrawal signs in rats-neurochemical and molecular basis in dopaminergic system.
abstract: Experimental data informs that not only do the dose and time duration of dependent drugs affect the severity of withdrawal episodes. Previous withdrawal experiences may intensify this process, which is referred as sensitization to withdrawal signs. Adenosine and dopamine (DA) receptors may be involved in this sensitization.
  
  
  
  Rats were continuously and sporadically treated with increasing doses of morphine for 8 days. In rats, sporadically treated with morphine, morphine administration was modified by adding three morphine-free periods. Adenosine agonists were given during each of the morphine-free periods (six injections in total). On the 9th day, morphine was injected. One hour later, naloxone was administered to induce morphine withdrawal signs. Then, the animals were placed into cylinders and the number of jumpings was recorded. Next, the rats were decapitated and brain and brain structures (striatum, hippocampus, and prefrontal cortex) were dissected for neurochemical, molecular, and immunohistochemical experiments within DAergic pathways.
  
  
  
  We demonstrated that previous experiences of opioid withdrawal intensified subsequent withdrawal signs. Adenosine ligands attenuated the sensitization to withdrawal signs. In a neurochemical study, the release of DA and its metabolites was impaired in all structures. Significant alterations were also observed in mRNA and protein expression of DA receptors.
  
  
  
  Results demonstrate that intermittent treatment with morphine induces alterations in the DAergic system which may be responsible for sensitization to morphine withdrawal signs. Although adenosine ligands attenuate this type of sensitization, they are not able to fully restore the physiological brain status.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093, Lublin, Poland. a.listos@umlub.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Listos
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Baranowska-Bosiacka
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12 St., 31-343, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Talarek
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences, Głęboka 30 St., 20-612, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Listos
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093, Lublin, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Łupina
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12 St., 31-343, Kraków, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24 St., 71-460, Szczecin, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Gutowska
authors.affiliation: Department of Physiology, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Tkacz
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pilutin
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093, Lublin, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Orzelska-Górka
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111, Szczecin, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chlubek
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D009270:Naloxone; D009020:Morphine; D000241:Adenosine; D004298:Dopamine
keywords: Dependence; Dopamine receptor expression; Morphine withdrawal signs; Naloxone