title: Functional striatal hypodopaminergic activity in mice lacking adenosine A(2A) receptors.
abstract: Adenosine and caffeine modulate locomotor activity and striatal gene expression, partially through the activation and blockade of striatal A(2A) receptors, respectively. The elucidation of the roles of these receptors benefits from the construction of A(2A) receptor-deficient mice (A(2A)-R(-/-)). These mice presented alterations in locomotor behaviour and striatal expression of genes studied so far, which are unexpected regarding the specific expression of A(2A) receptor by striatopallidal neurones. To clarify the functions of A(2A) receptors in the striatum and to identify the mechanisms leading to these unexpected modifications, we studied the basal expression of immediate early and constitutive genes as well as dopamine and glutamate neurotransmission in the striatum. Basal zif268 and arc mRNAs expression was reduced in mutant mice by 60-80%, not only in the striatum but also widespread in the cerebral cortex and hippocampus. Striatal expression of substance P and enkephalin mRNAs was reduced by about 50% and 30%, respectively, whereas the expression of GAD67 and GAD65 mRNAs was slightly increased and unaltered, respectively. In vivo microdialysis in the striatum revealed a 45% decrease in the extracellular dopamine concentration and three-fold increase in extracellular glutamate concentration. This was associated with an up-regulation of D(1) and D(2) dopamine receptors expression but not with changes in ionotropic glutamate receptors. The levels of tyrosine hydroxylase and of striatal and cortical glial glutamate transporters as well as adenosine A(1) receptors expression were indistinguishable between A(2A)-R(-/-) and wild-type mice. Altogether these results pointed out that the lack of A(2A) receptors leads to a functional hypodopaminergic state and demonstrated that A(2A) receptors are necessary to maintain a basal level in immediate early and constitutive genes expression in the striatum and cerebral cortex, possibly via their control of dopamine pathways.
authors: European Graduate School of Neuroscience (EURON), Laboratory of Neurophysiology, Department of Neuroscience, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, 1070 Brussels, Belgium. Donald.Dassesse@ulb.ac.be
authors: D
authors: D
authors: Dassesse
authors: A
authors: A
authors: Massie
authors: R
authors: R
authors: Ferrari
authors: C
authors: C
authors: Ledent
authors: M
authors: M
authors: Parmentier
authors: L
authors: L
authors: Arckens
authors: M
authors: M
authors: Zoli
authors: S N
authors: SN
authors: Schiffmann
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000172:deficiency / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D004745:Enkephalins; D007527:Isoenzymes; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D013373:Substance P; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D004298:Dopamine