title: Behavioral impairments and serotonin reductions in rats after chronic L-dopa.
abstract: BACKGROUND
  L-dopa, the main therapeutic for Parkinson's disease (PD), has been shown to increase brain dopamine concentrations that are necessary for proper motor control; however, PD patients experience non-motor symptoms that are not improved or could be exacerbated by L-dopa.
  
  
  OBJECTIVE
  The purpose of this study is to determine the effects of L-dopa treatment on cognitive and affective behavioral responses of rats, as well as their corresponding monoamine brain concentrations.
  
  
  METHODS
  Rats were treated with L-dopa (6 mg/kg; twice daily) for 10 consecutive days. Sodium ascorbate (400 mg/kg) was co-administered with L-dopa to investigate the effects of antioxidant co-treatment on behavior and monoamine concentrations. Rats underwent cognitive and affective behavioral testing. Monoamine concentrations of several brain regions were analyzed.
  
  
  RESULTS
  L-dopa treatment resulted in significant impairment in the performance in the Barnes maze and improvement in conditioned fear stress paradigms. Specifically, L-dopa caused an increase in latency to find the goal box during Barnes maze testing and increased freezing behavior in context-induced conditioned fear testing. Furthermore, the rats in the conditioned fear stress experiments showed corresponding depletions in serotonin (5-HT) and its metabolite, 5-HIAA, in the dorsal raphe nucleus (DRN) and the mPFC. The behavioral impairments as well as monoamine depletions were blocked by ascorbate co-treatment.
  
  
  CONCLUSIONS
  Chronic L-dopa may contribute to non-motor symptoms related to spatial memory and fear. These effects may be attributable to a dysregulation of brain 5-HT caused by L-dopa treatment. The results presented here provide further rationale for investigating adjunctive therapeutics to L-dopa for PD, such as antioxidants.
authors.affiliation: Department of Neurosciences, University of Toledo College of Medicine, 3000 Arlington Avenue, Mail Stop 1007, Toledo, OH, 43614, USA.
authors.forename: Branden J
authors.initials: BJ
authors.lastname: Stansley
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Yamamoto
mesh_terms: D000339:Affect / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D005239:Fear / Q000523:psychology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D015306:Biogenic Monoamines; D015259:Dopamine Agents; D012702:Serotonin Antagonists; D012701:Serotonin; D007980:Levodopa; D001205:Ascorbic Acid