Behavioral impairments and serotonin reductions in rats after chronic L-dopa

Branden J. Stansley, Bryan K. Yamamoto

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Rationale: 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. Objectives: 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.

Original languageEnglish (US)
Pages (from-to)3203-3213
Number of pages11
Issue number17
StatePublished - Sep 14 2015
Externally publishedYes


  • Barnes maze
  • Conditioned fear stress
  • L-dopa
  • Parkinson's disease
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

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