Adenosine A2A receptors are expressed by GABAergic neurons of medulla oblongata in developing rat

During early development, adenosine contributes to the occurrence of respiratory depression and recurrent apneas. Recent physiological studies indicate that GABAergic mechanisms may be involved in this inhibitory action of adenosine, via their A2A receptors. In the present study, in situ hybridization with ribonucleotide probes for A2A receptor (A2AR) mRNA was combined with the immunolabeling technique for parvalbumin and transneuronal retrograde tracing method using green fluorescent protein expressing pseudorabies virus (GFP-PRV) to (1) characterize age-dependent changes in the expression of adenosine A2ARs mRNA in brain stem regions where GABAergic neurons are located; (2) determine whether GABA-containing neurons express A2AR mRNA traits, and (3) identify whether bulbospinal GABAergic neurons projecting to phrenic nuclei contain A2AR mRNA. Results revealed expression of A2A receptors in regions of medulla oblongata containing GABAergic neurons, namely in the ventral aspect of the medulla, within the Bötzinger region and caudal to it, the gigantocellular reticular nucleus, midline neurons and the caudal ventrolateral medulla oblongata. Furthermore, a subpopulation of identified GABAergic neurons, projecting to the phrenic motor nuclei, possess A2AR mRNA. It is concluded that adenosine A2ARs expressed by GABAergic neurons are likely to play a role in mediating adenosine-induced respiratory depression.