Differential regulation of adenosine A1 and A2A receptors in serotonin transporter and monoamine oxidase A-deficient mice |
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Authors: | Rainald Mssner 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 |
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Institution: | 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 |
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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 A2A receptors. A1 and A2A 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 A2A receptors in basal ganglia. The adaptive changes of A1 and A2A 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 A2A receptors similar to 5HTT knockout mice, while investigation of MAOA-deficient mice revealed an upregulation of A2A receptors, which may relate to a role of both MAOA and adenosine A2A receptors in anxiety. |
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Keywords: | Serotonin transporter Adenosine A1 receptor Adenosine A2A receptor Dorsal raphe nucleus Accumbens nucleus Monoamine oxidase A Knockout mouse Autoradiography |
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