title: Tremorolytic effect of 5'-chloro-5'-deoxy-(±)-ENBA, a potent and selective adenosine A1 receptor agonist, evaluated in the harmaline-induced model in rats.
abstract: OBJECTIVE
  The aim of this study was to examine the role of adenosine A1receptors in the harmaline-induced tremor in rats using 5'-chloro-5'-deoxy-(±)-ENBA (5'Cl5'd-(±)-ENBA), a brain-penetrant, potent, and selective adenosine A1receptor agonist.
  
  
  METHODS
  Harmaline was injected at a dose of 15 mg/kg ip and tremor was measured automatically in force-plate actimeters by an increased averaged power in the frequency band of 9-15 Hz (AP2) and by tremor index (a difference in power between AP2 and averaged power in the frequency band of 0-8 Hz). The zif-268 mRNA expression was additionally analyzed by in situ hybridization in several brain structures.
  
  
  RESULTS
  5'Cl5'd-(±)-ENBA (0.05-0.5 mg/kg ip) dose dependently reduced the harmaline-induced tremor and this effect was reversed by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of adenosine A1receptors (1 mg/kg ip). Harmaline increased the zif-268 mRNA expression in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei, and motor cortex. 5'Cl5'd-(±)-ENBA reversed these increases in all the above structures. DPCPX reduced the effect of 5'Cl5'd-(±)-ENBA on zif-268 mRNA in the motor cortex.
  
  
  CONCLUSIONS
  This study suggests that adenosine A1receptors may be a potential target for the treatment of essential tremor.
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kosmowska
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Krystyna
authors.identifier: http://orcid.org/0000-0002-8381-6632
authors.initials: K
authors.lastname: Ossowska
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Głowacka
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Jadwiga
authors.identifier: http://orcid.org/0000-0002-0208-1946
authors.initials: J
authors.lastname: Wardas
mesh_terms: D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D006246:Harmaline; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000378:metabolism; D009636:Norbornanes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D014202:Tremor / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: C000618732:5'-chloro-5'-deoxy-N6-(norborn-2-yl)adenosine; D058907:Adenosine A1 Receptor Agonists; D003839:Deoxyadenosines; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009636:Norbornanes; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D006246:Harmaline
keywords: adenosine A1 receptor agonist; essential tremor; harmaline; tremorolytic effect; zif-268