Annual Meeting of the Society for Neuroscience edition:31 location:San Diego, U.S.A. date:November 10-15, 2001
Adenosine and caffeine modulate locomotor activity and striatal gene expression, partially through activation and blockade of striatal A2A-R, respectively. A2A-R-/- mice presented unexpected alterations in locomotor behaviour regarding the specific expression of A2A-R in striatopallidal neurons. To clarify the functions of A2A-R 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 neurotransmission in the striatum.
Basal zif-268 and arc mRNAs expression was reduced in mutant mice by 60-80%, in the striatum but also widespreadly 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. This was associated with an up-regulation of D1 and D2 dopamine receptors expression.
Altogether these results pointed out that the lack of A2A-R leads to a functional hypodopaminergic state and demonstrated that A2A-R 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.