TY - JOUR
T1 - Differential regulation of adenosine A1 and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice
AU - Mössner, Rainald
AU - Albert, Dietmar
AU - Persico, Antonio M.
AU - Hennig, Thomas
AU - Bengel, Dietmar
AU - Holtmann, Bettina
AU - Schmitt, Angelika
AU - Keller, Flavio
AU - Simantov, Rabi
AU - Murphy, Dennis
AU - Seif, Isabelle
AU - Deckert, Jürgen
AU - Lesch, K. Peter
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Accumbens nucleus
KW - Adenosine A(2A) receptor
KW - Adenosine A receptor
KW - Autoradiography
KW - Dorsal raphe nucleus
KW - Knockout mouse
KW - Monoamine oxidase A
KW - Serotonin transporter
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U2 - 10.1016/S0924-977X(00)00119-X
DO - 10.1016/S0924-977X(00)00119-X
M3 - Article
C2 - 11115739
AN - SCOPUS:0033673924
VL - 10
SP - 489
EP - 493
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
IS - 6
ER -