Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus

We examined the effects of adenosine and baclofen on inhibitory (IPSC) and excitatory (EPSC) synaptic currents in dissociated rat hippocampal neurons. Adenosine dramatically reduced monosynaptic EPSCs but failed to diminish IPSCs. This selective effect on EPSCs is likely due to inhibition of excitatory transmitter release because adenosine did not directly alter any properties of postsynaptic neurons. Baclofen depressed both EPSCs and IPSCs to approximately the same extent. These experiments indicate that the presynaptic effects of adenosine and baclofen are clearly separable and that transmitter sensitivities of inhibitory and excitatory neurons can differ. These differences could be exploited in the design of antiepileptic drugs that act at adenosine receptors to limit excitatory neurotransmission without blocking tonic inhibition.