Differential regulation of adenosine A1 and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice

Rainald Mössner, Dietmar Albert, Antonio M. Persico, Thomas Hennig, Dietmar Bengel, Bettina Holtmann, Angelika Schmitt, Flavio Keller, Rabi Simantov, Dennis Murphy, Isabelle Seif, Jürgen Deckert, K. Peter Lesch

Research output: Contribution to journalArticlepeer-review

Abstract

The serotonin (5HT) transporter (5HTT) removes 5HT from the synaptic cleft and is thus critical to the control of serotonergic neurotransmission. Mice with a targeted inactivation of the 5HTT represent a novel and unique tool to study serotonergic system functioning. Because the release of 5HT is regulated by adenosine, we investigated 5HTT-deficient mice for possible adaptive changes of adenosine A1 and A(2A) receptors. A1 and A(2A) receptors were studied by means of quantitative autoradiography using the radioligands [3H]8-cyclopentyl-1,3-dipropylxanthine and [3H]CGS 21680, respectively. A comparison of 5HTT knockout versus control mice revealed upregulation of A1 receptors in the dorsal raphe nucleus (DRN, +21%), but not in any of the serotonergic projection areas, and downregulation of A(2A) receptors in basal ganglia. The adaptive changes of A1 and A(2A) receptors in 5HTT-deficient mice are likely to represent a compensatory neuroprotective effect mediated by the adenosinergic modulatory system. For comparison, these receptors were also studied in monoamine oxidase A (MAOA) knockout mice and in 5HTT/MAOA double knockout mice. 5HTT/MAOA double knockout mice showed adaptive changes of adenosine A1 and A(2A) receptors similar to 5HTT knockout mice, while investigation of MAOA-deficient mice revealed an upregulation of A(2A) receptors, which may relate to a role of both MAOA and adenosine A(2A) receptors in anxiety. Copyright (C) 2000 Elsevier Science B.V./ECNP.

Original languageEnglish
Pages (from-to)489-493
Number of pages5
JournalEuropean Neuropsychopharmacology
Volume10
Issue number6
DOIs
Publication statusPublished - 2000

Keywords

  • Accumbens nucleus
  • Adenosine A(2A) receptor
  • Adenosine A receptor
  • Autoradiography
  • Dorsal raphe nucleus
  • Knockout mouse
  • Monoamine oxidase A
  • Serotonin transporter

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)

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