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Subchronic elevation of brain kynurenic acid augments amphetamine-induced locomotor response in mice

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The neuromodulating tryptophan metabolite kynurenic acid (KYNA) is increased in the brain of patients with schizophrenia. In the present study we investigate the spontaneous locomotor activity as well as the locomotor response to d-amphetamine [5 mg/kg, administered intraperitoneal (i.p.)] after increasing endogenous levels of brain KYNA in mice by acute (10 mg/kg, i.p., 60 min) or subchronic (100 mg/kg i.p., twice daily for 6 days) pretreatment with the blood–brain crossing precursor, l-kynurenine. We found that an acute increase in the brain KYNA levels caused increased corner time and percent peripheral activity but did not change the d-amphetamine-induced locomotor response. In contrast, subchronic elevation of KYNA did not change the spontaneous locomotor activity but produced an exaggerated d-amphetamine-induced hyperlocomotion. These results cohere with clinical studies of patients with schizophrenia, where a potentiated DA release associated with exacerbation of positive symptoms has been observed following d-amphetamine administration. Present results further underscore KYNA as a possible mediator of the aberrant dopaminergic neurotransmission seen in schizophrenia.

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Acknowledgments

Financial support for this study was provided by the Karolinska Institutet, Svenska Läkaresällskapet and the Swedish Research Council (Dr. Erhardt, No. 2009-4046; 2009-7052).

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The authors declare that they have no conflict of interest.

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  1. Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, 171 77, Stockholm, Sweden

    Sara K. Olsson, Markus K. Larsson & Sophie Erhardt

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  1. Sara K. Olsson
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  2. Markus K. Larsson
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  3. Sophie Erhardt
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Correspondence to Sophie Erhardt.

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Olsson, S.K., Larsson, M.K. & Erhardt, S. Subchronic elevation of brain kynurenic acid augments amphetamine-induced locomotor response in mice. J Neural Transm 119, 155–163 (2012). https://doi.org/10.1007/s00702-011-0706-6

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  • DOI: https://doi.org/10.1007/s00702-011-0706-6

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