Ultrastructural localization of adenosine A(2A) receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum

Activation of adenosine A(2A) receptors (A(2A)R) has been shown to antagoni ze the function of D-2 dopaminergic regulation of striatal gamma -aminobuty ric acid (GABA)-ergic output and, thus, locomotor activity. Adenosine A(2A) receptor immunoreactivity (A(2A)-LI) has been localized to rat striatum by light microscopy by using a previously characterized human A(2A)R monoclon al antibody. In this study, we evaluated the localization of A(2A)-LI and i ts colocalization with GABA immunoreactivity (GABA-LI) in dorsolateral rat striatum by immunoelectron microscopy to further characterize the potential mechanism of purinergic control of striatal output. Ultrastructural analys is demonstrated A(2A)-LI associated with the plasma membrane and cytoplasmi c membranous structures of striatal neurons. A(2A)-LI was prevalent in dend rites and dendritic spines (similar to 70% of total A(2A)-profiles counted) and less prevalent in axons and axon terminals (23%), soma (3%), and glia (3%). Cellular elements exhibiting both A(2A)-LI and GABA-LI comprised 23% of the total profiles counted; colabeling was most common in dendrites. A(2 A)-LI was observed primarily at asymmetric synapses (n = 70) (both pre- and postsynaptically but predominantly in the postsynaptic element) and less f requently at symmetric synapses (n = 17). Of the 714 A(2A)-immunoreactive p rofiles examined, 37% were apposed to GABA-labeled profiles. The most commo n appositions were A(2A)-labeled dendrites apposed to GABA-immunoreactive d endrites (n = 132), axon terminals (n = 28), and somata (n = 22) and A(2A)- labeled axons apposed to GABA-labeled dendrites (n = 58), axon terminals (n = 14), and somata (n = 9). Our findings suggest that adenosine may play an important role in modulating excitatory input to striatal neurons and that A(2A)R may modulate GABAergic signaling at several cellular sites within t he rat striatum.