Activation of adenosine A1 receptors initiates short-term synaptic depression in rat striatum

High-frequency stimulation (HFS) of afferent fibers produced short-term depression (STD) and long-term depression (LTD) of corticostriatal synaptic transmission. Application of the non-selective adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) or the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the induction of STD but not LTD. Application of adenosine or the selective A1 receptor agonist R(-)N6-(2-phenylisopropyl)adenosine (R-PIA) induced synaptic depression, while the A2a receptor agonist CGS 21680 did not consistently alter synaptic transmission. Depression induced by adenosine or R-PIA was not accompanied by changes in postsynaptic input resistance and appeared to involve a presynaptic depressant effect previously characterized at this synapse. These observations indicate that HFS leads to the production of endogenous adenosine that acts on presynaptic A1 receptors to initiate STD at corticostriatal synapses. Initiation and maintenance of LTD appear to be independent of A1 receptor activation.