Cellular distribution of adenosine A2A receptor mRNA in the primate striatum

The cellular expression of adenosine A2A receptor mRNA in the adult monkey and human striatum was examined by using single and double in situ hybridization with ribonucleotide probes. Analysis on adjacent sections demonstrated a homogeneous overlapping expression of adenosine A2A receptor and preproenkephalin A mRNAs throughout nucleus caudatus, putamen, and nucleus accumbens. By contrast, high expression of preproenkephalin A mRNA but no expression of adenosine A2A receptor mRNA was found in the nucleus basalis of Meynert. Double in situ hybridization demonstrated an extensive colocalization of adenosine A2A receptor and preproenkephalin A mRNAs in approximately 50% of the medium-sized spiny neurons of the monkey nucleus caudatus, putamen, and nucleus accumbens. A small number of neurons (4-12%) that contained adenosine A2A receptor mRNA but not preproenkephalin A mRNA was found along the ventral borders of the striatum. Virtually all adenosine A2A receptor mRNA-containing neurons co-expressed dopamine D2 receptor mRNA, whereas only very few adenosine A2A receptor mRNA containing neurons co-expressed dopamine D1 receptor or substance P mRNAs. In addition, a sub-population of adenosine A2A receptor mRNA-expressing neurons that also contained preproenkephalin A mRNA was found in the septum in monkeys. These results demonstrate that there is a high expression of adenosine A2A receptor mRNA in the primate striatum that is extensively co-localized with dopamine D2 receptor and preproenkephalin A mRNAs. It is concluded that adenosine A2A receptors are likely to be important for the parallel organization of primate striatal neurotransmission and that these receptors could be a target for drug therapy in Parkinson's disease.