Adenosine A1 receptor-mediated depression of corticostriatal and thalamostriatal glutamatergic synaptic potentials in vitro.

Electrophysiological recordings in rat brain slices have been used to study the actions of adenosine on striatal neurons and striatal excitatory amino acid neurotransmission originating in the cortex or the thalamus. Adenosine had no effects on membrane properties of striatal neurons. Adenosine and the A1 agonist N6-Cyclopentyl adenosine reduced EPSPs of both cortical and thalamic origin by more than 50%. Depression of EPSPs was associated with an increase in paired-pulse facilitation, suggesting a presynaptic locus of action. EPSP depression was blocked by the A1 antagonist, 8-Cyclopentyl-1,3-dipropyl xanthine. The A2 agonist 5'-(N-cyclopropyl)-carboxamidoadenosine had no effect on excitatory amino acid neurotransmission. The A1 antagonist alone enhanced the synaptic component of the evoked field potential (23 +/- 12%). These results indicate that endogenous adenosine, acting via A1 receptors, limits striatal glutamatergic neurotransmission, serving a modulatory and neuroprotective role.