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Adenosine and ATP, via their specific P1 and P2 receptors, modulate a wide variety of cellular and tissue functions, playing a neuroprotective or neurodegenerative role in brain damage conditions. Although, in general, adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, recent data suggest the existence of a heterodimerization and a functional interaction between P1 and P2 receptors in the brain. In particular, interactions of adenosine A₁ and P2Y₁ receptors may play important roles in the purinergic signalling cascade. In the present work, we investigated the subcellular localization/co‐localization of the receptors and their functional cross‐talk at the membrane level in Wistar rat hippocampus. This is a particularly vulnerable brain area, which is sensitive to adenosine‐ and ATP‐mediated control of glutamatergic transmission. The postembedding immunogold …