title: Antidepressant-like properties of sarizotan in experimental Parkinsonism.
abstract: BACKGROUND
  Depression and anxiety are common symptoms in Parkinson's disease for which there are no optimal treatments. Sarizotan, an agonist at serotonin receptors and partial agonist at dopamine D₂-like receptors, has shown antidyskinetic effects in Parkinson's disease. Based on its pharmacological profile, we hypothesized that sarizotan could also have antidepressant-like properties.
  
  
  OBJECTIVE
  Examine effects of sarizotan on behavioral and histological measures known to be regulated by established antidepressants in normal and unilaterally 6-hydroxydopamine-lesioned rats.
  
  
  RESULTS
  Sarizotan was found to significantly reduce immobility in the modified forced swim test, a measure of antidepressant-like activity, but had no effects on thigmotaxis or corner time, measures of anxiety-like behavior, in the unilaterally 6-hydroxydopamine-lesioned rats. At the same dose, sarizotan counteracted L: -DOPA/benserazide-induced supersentitized rotational behavior and dyskinesias without significantly affecting L: -DOPA/benserazide-induced locomotion. At the histological level, sarizotan alone or in combination with L: -DOPA/benserazide stimulated cell proliferation, measured by bromodeoxyuridine incorporation or Ki-67 staining, both in the subgranular zone of the dentate gyrus and in the subventricular zone of the striatum in the 6-hydroxydopamine-lesioned hemisphere. Likewise, combined sarizotan and L: -DOPA/benserazide treatment stimulated doublecortin levels in the subgranular zone of the dentate gyrus.
  
  
  CONCLUSIONS
  These significant effects of sarizotan in the modified forced swim test and on cell proliferation are reminiscent of those found after various antidepressant therapies. These data suggest that sarizotan may have some antidepressant-like and restorative properties in Parkinsonism.
authors.affiliation: Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.forename: Martin
authors.initials: M
authors.lastname: Egeland
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001545:Benserazide / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004338:Drug Combinations; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009930:Organic Chemicals / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D000978:Antiparkinson Agents; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D004338:Drug Combinations; D009930:Organic Chemicals; C005177:benserazide, levodopa drug combination; D007980:Levodopa; C443959:sarizotan; D001545:Benserazide