title: The MAO-B inhibitor deprenyl reduces the oral tremor and the dopamine depletion induced by the VMAT-2 inhibitor tetrabenazine.
abstract: Tetrabenazine (TBZ) is prescribed for the treatment of chorea associated with Huntington's disease. Via inhibition of the vesicular monoamine transporter (VMAT-2), TBZ blocks dopamine (DA) storage and depletes striatal DA; this drug also has been shown to induce Parkinsonian motor side effects in patients. Recently, TBZ was shown to induce tremulous jaw movements (TJMs) in rats and mice. TJMs are an oral tremor that has many of the characteristics of Parkinsonian tremor in humans. The present study focused upon the ability of the well-established antiparkinsonian agent deprenyl to attenuate the behavioral and neurochemical effects of 2.0mg/kg TBZ. Deprenyl is a selective and irreversible inhibitor of monoamine oxidase-B, and administration of deprenyl produced a dose-related suppression of TBZ-induced TJMs. A second experiment employed in vivo microdialysis to examine extracellular DA levels in the ventrolateral striatum, the neostriatal region most closely associated with the production of TJMs, after administration of TBZ and deprenyl. Consistent with the behavioral data, TBZ alone produced a biphasic effect on extracellular DA, with an initial increases followed by a prolonged decrease during the period in which TJMs are displayed. Co-administration of deprenyl with TBZ increased DA levels compared to rats treated with TBZ alone. These results provide support for use of TBZ as a rodent model of Parkinsonism, and future studies should utilize this model to evaluate putative anti-Parkinsonian agents.
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Podurgiel
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Yohn
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Dortche
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA; Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Merce
authors.initials: M
authors.lastname: Correa
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. Electronic address: john.salamone@uconn.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007568:Jaw; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013747:Tetrabenazine / Q000494:pharmacology / Q000633:toxicity*; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D012642:Selegiline; D004298:Dopamine; D013747:Tetrabenazine