title: Side effect profile of 5-HT treatments for Parkinson's disease and L-DOPA-induced dyskinesia in rats.
abstract: OBJECTIVE
  Treatment of Parkinson's disease (PD) with L-DOPA eventually causes abnormal involuntary movements known as dyskinesias in most patients. Dyskinesia can be reduced using compounds that act as direct or indirect agonists of the 5-HT1 A receptor, but these drugs have been reported to worsen PD features and are known to produce '5-HT syndrome', symptoms of which include tremor, myoclonus, rigidity and hyper-reflexia.
  
  
  METHODS
  Sprague-Dawley rats were given unilateral nigrostriatal dopamine lesions with 6-hydroxydopamine. Each of the following three purportedly anti-dyskinetic 5-HT compounds were administered 15 min before L-DOPA: the full 5-HT1 A agonist ±-8-hydroxy-2-dipropylaminotetralin (±8-OH-DPAT), the partial 5-HT1 A agonist buspirone or the 5-HT transporter inhibitor citalopram. After these injections, animals were monitored for dyskinesia, 5-HT syndrome, motor activity and PD akinesia.
  
  
  RESULTS
  Each 5-HT drug dose-dependently reduced dyskinesia by relatively equal amounts (±8-OH-DPAT ≥ citalopram ≥ buspirone), but 5-HT syndrome was higher with ±8-OH-DPAT, lower with buspirone and not present with citalopram. Importantly, with or without L-DOPA, all three compounds provided an additional improvement of PD akinesia. All drugs tempered the locomotor response to L-DOPA suggesting dyskinesia reduction, but vertical rearing was reduced with 5-HT drugs, potentially reflecting features of 5-HT syndrome.
  
  
  CONCLUSIONS
  The results suggest that compounds that indirectly facilitate 5-HT1 A receptor activation, such as citalopram, may be more effective therapeutics than direct 5-HT1 A receptor agonists because they exhibit similar anti-dyskinesia efficacy, while possessing a reduced side effect profile.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, Binghamton University - State University of New York, Binghamton, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lindenbach
authors.forename: N
authors.initials: N
authors.lastname: Palumbo
authors.forename: C Y
authors.initials: CY
authors.lastname: Ostock
authors.forename: N
authors.initials: N
authors.lastname: Vilceus
authors.forename: M M
authors.initials: MM
authors.lastname: Conti
authors.forename: C
authors.initials: C
authors.lastname: Bishop
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000627:therapeutic use*; D000818:Animals; D000978:Antiparkinson Agents; D002065:Buspirone / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D007980:Levodopa; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011597:Psychomotor Performance; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*
chemical_list: D000978:Antiparkinson Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D007980:Levodopa; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone