Cellular expression of adenosine A 2A receptor messenger RNA in the rat central nervous system with special reference to dopamine innervated areas

Abstract

The cellular distribution of adenosine A 2A receptor messenger RNA in the central nervous system was investigated using in situ hybridization with ribonucleotide probes. A specific expression was found in the dorsal (i.e. caudate–putamen) and ventral (i.e. nucleus accumbens and olfactory tubercle) striatum, the lateral septum and in some cerebellar Purkinje cells. Simultaneous detection of radioactive and non-radioactive probes showed that the majority of adenosine A 2A receptor messenger RNA-containing neurons in the dorsal and ventral striatum co-expressed dopamine D 2 receptor messenger RNA and preproenkephalin A messenger RNA. However, a minor sub-population of neurons expressing adenosine A 2A receptor messenger RNA, but not preproenkephalin A messenger RNA, was found in clusters along the ventral border of the nucleus accumbens. Only a small number of striatal neurons expressing dopamine D 1 receptor or substance P messenger RNAs also expressed adenosine A 2A receptor messenger RNA. Finally, in the ventral part of nucleus accumbens and in the olfactory tubercle a major sub-population of neurons expressed preproenkephalin A messenger RNA, but not adenosine A 2A receptor messenger RNA. Cholinergic interneurons did not express adenosine A 2A receptor messenger RNA. Thus, the extensive co-localization of adenosine A 2A and dopamine D 2 receptors previously described in the dorsal striatum extends into its ventral part. There is also a high degree of co-expression of adenosine A 2A receptor messenger RNA and preproenkephalin A messenger RNA in the ventral striatum, but within this region several topologically defined sub-populations of neurons express only one of these transcripts. A majority of the adenosine A 2A receptor messenger RNA-containing neurons in the lateral septum did contain preproenkephalin A messenger RNA, whereas only a few co-expressed dopamine D 2 receptor messenger RNA. This detailed investigation demonstrates that most of the subcortical areas innervated by dopamine have an abundant, although restricted expression of the adenosine A 2A receptor gene and that this receptor is expressed in very few cells outside these areas. These results predict that adenosine A 2A receptors are involved not only in motor behaviour, but also in goal-oriented behaviours.