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Nigrostriatal cell firing action on the dopamine transporter

Authors

  • Manuel Rodriguez,

    1. Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine,
    2. Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, CIBERNED
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  • Sergio Gonzalez,

    1. Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine,
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  • Ingrid Morales,

    1. Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine,
    2. Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, CIBERNED
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  • Magdalena Sabate,

    1. Department of Pharmacology and Physical Medicine and
    2. Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, CIBERNED
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  • Tomas Gonzalez-Hernandez,

    1. Department of Anatomy, Faculty of Medicine, University of La Laguna, La Laguna, 38320 Tenerife, Canary Islands, Spain
    2. Centro de Investigación en Red sobre Enfermedades Neurodegenerativas, CIBERNED
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  • Jose Luis Gonzalez-Mora

    1. Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine,
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Dr Manuel Rodríguez, as above.
E-mail: mrdiaz@ull.es

Abstract

The influence of nigrostriatal cell firing on the dopamine transporter (DAT) activity of the rat striatum was studied in vivo with amperometric methods. Data were obtained after preventing dopamine (DA) release with α-methyl-l-tyrosine and replenishing extracellular DA with local injections. The DA cell stimulation, which under basal conditions increased extracellular DA, decreased DA after this pre-treatment, suggesting that firing activity facilitates the DA cell uptake of DA under these circumstances (drain response). Cocaine and GBR13069 markedly decreased the drain response, suggesting that it is dependent on DAT activation. Data obtained after haloperidol and apomorphine administration showed that the drain response was facilitated by pre-synaptic DA receptor stimulation but that receptors are not a necessary requirement. Two components in the drain response were observed, one with a short latency and duration that needed high-frequency stimuli, and the other with a long latency and duration that was even induced by low-frequency stimuli. This is the first evidence showing that DAT can be activated by the firing activity in nigrostriatal cells in a direct way and without the participation of pre-synaptic DA receptors.

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