A role for adenosine A 2 receptors in the induction of long-term potentiation in the CA1 region of rat hippocampus

Abstract

Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A 1 receptor activation, the implications of A 2 receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A 2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A 2 receptor blockade in the presence of complete A 1 receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A 2 receptors can enhance synaptic transmission. A 2 receptor blockade by the A 2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A 1 receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A 1 receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A 2 antagonist 8-SPT (8-( p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A 2 receptors play no significant role in the maintenance phase of LTP. Selective A 2a receptor activation did not alter the field EPSP. Similarly, selective blockade of the A 2a receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A 2 receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A 2b receptor.