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Journal of Molecular Neuroscience

, Volume 26, Issue 2–3, pp 239–244 | Cite as

Adenosine-dopamine interactions revealed in knockout mice

  • Peter Salmi
  • Karima Chergui
  • Bertil B. Fredholm
Review

Abstract

Neurochemical and pharmcological evidence obtained over the past 300 yr has indicated that adenosine and dopamine interact functionally in the basal ganglia and that such interactions have pathophysiological and theraputic implications. The receptors implicated are adenosine A1 and A2A, and dopamine D1 and D2. There is evidence that dopamine D2 receptor activation in vivo antagonizes tonic activation of adenosine A2A receptors. Thus, acute blockade of dopamine D2 receptors, or disruption of dopamine transmission, unmasks strong adenosine A2A activation. Effects of dopamine D2 blockade are different after adenosine A2A blockade or in A2A knockout mice. Possibly as an adaptation to this increase in adenosine A2A signaling, there is a decreased coupling of A2A receptors to biological effects in dopamine D2 knockout mice. Compared to wild-type mice, adenosine A2A knockout mice show decreased neurodegeneration after treatment with 1-myeyl-1,2,3,6-tetrahydropyridine (MPTP) and show improved motor performance in models of Parkinson’s disease Adenosine A1 receptors are not spccifically located with any dopamine receptor, as is the A2A receptor with D2 receptors. Many A1 receptors are located presynaptically, where they regulate transmitter release. In A1 knockout mice, glutamatergic and dopaminergic transmission is therefore modified.

Index Entries

Adenosine dopamine caffeine knockout mouse 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Peter Salmi
    • 1
  • Karima Chergui
    • 1
  • Bertil B. Fredholm
    • 1
  1. 1.Department of Physiology and PharmacologyKarolinska InstitutetStockholmSweden

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