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

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Abstract

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.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurosciences, University of Toledo College of Medicine, 3000 Arlington Avenue, Mail Stop 1007, Toledo, OH, 43614, USA

    Branden J. Stansley & Bryan K. Yamamoto

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  1. Branden J. Stansley
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  2. Bryan K. Yamamoto
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Correspondence to Bryan K. Yamamoto.

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Research supported by NIDA: DA007606

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Stansley, B.J., Yamamoto, B.K. Behavioral impairments and serotonin reductions in rats after chronic L-dopa. Psychopharmacology 232, 3203–3213 (2015). https://doi.org/10.1007/s00213-015-3980-4

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  • DOI: https://doi.org/10.1007/s00213-015-3980-4

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