title: The D₂ dopamine receptor and locomotor hyperactivity following bilateral vestibular deafferentation in the rat.
abstract: Rats and mice with bilateral vestibular loss exhibit dramatic locomotor hyperactivity and circling behaviours, which to date cannot be explained. Dysfunction of the striatal dopaminergic system is responsible for a number of known movement disorders and the D(2) dopamine receptor is known to be implicated. Therefore, it is possible that changes in striatal function are responsible for locomotor hyperactivity and circling following bilateral vestibular lesions. The aim of this study was to investigate the effects of the D(2) receptor antagonist, eticlopride (0.02, 0.04 and 0.06mg/kg; s.c.), on locomotor behaviour in rats at 5 months following bilateral vestibular deafferentation (BVD), using an open field maze. The levels of the D(2) receptor protein in the striatum were measured at 1 and 6 months post-BVD using western blotting. BVD rats exhibited locomotor hyperactivity and circling, which eticlopride did not eliminate. However, BVD rats did exhibit a decreased response to the inhibitory effect of eticlopride compared to sham controls at the 0.02 mg/kg dose. There were no changes in the amount of the D(2) receptor in the striatum at 1 or 6 months post-BVD; however, D(2) receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that locomotor hyperactivity and circling behaviours following BVD are not due simply to changes in D(2) receptor protein expression in the striatum and that other neurophysiological changes in the brain account for these behaviours following BVD.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medical Sciences, and the Brain Health Research Centre, University of Otago Medical School, Dunedin, New Zealand.
authors.forename: Lucy
authors.initials: L
authors.lastname: Stiles
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zheng
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Darlington
authors.forename: Paul F
authors.initials: PF
authors.lastname: Smith
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D006948:Hyperkinesis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013997:Time Factors; D014722:Vestibule, Labyrinth / Q000293:injuries*
chemical_list: D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C045989:eticlopride