A functional role for adenosine A3 receptors: modulation of synaptic plasticity in the rat hippocampus

Adenosine modulates hippocampal synaptic plasticity, namely long-term potentiation (LTP) and long-term depression (LTD), through activation of A1 and A2A receptors. We now report a novel role for the recently described adenosine A3 receptor in the regulation of synaptic plasticity in the CA1 area of hippocampal slices. Activation of adenosine A3 receptors by (1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-p-yl]-1-deoxy-N-methyl-beta-D-ribofuranuronamide (Cl-IBMECA) (100 nM) increased the magnitude of theta-burst induced LTP (from 1.2+/-0.6% in the control solution to 25.5+/-0.8% in the presence of Cl-IBMECA) and attenuated LTD (from 30.0+/-5.5% decrease in the control solution to 13.6+/-6.6% decrease in the presence of Cl-IBMECA). The selective adenosine A3 receptor antagonist, MRS 1191 (5-10 microM), prevented the effects of Cl-IBMECA. These findings indicate a functional role for adenosine A3 receptors in the modulation of synaptic plasticity.