THE CONTRIBUTION OF ADENOSINE TO PAIRED-PULSE INHIBITION IN THE NORMAL AND DISINHIBITED HIPPOCAMPAL SLICE

The effects of the adenosine receptor antagonist 1,3-dimethyl-8-cyclop entylxanthine (cyclopentyltheophylline) and the enzyme adenosine deami nase have been examined on paired-pulse inhibition between orthodromic evoked field potentials in the CA1 region of the normal and disinhibi ted hippocampal slice. In the presence of the GABA(A) receptor antagon ist (-)-bicuculline methobromide, cyclopentyltheophylline suppressed h omosynaptic paired-pulse inhibition between stimuli 300 ms apart. Slic es treated with (-)-bicuculline and cyclopentyltheophylline together t ended to develop spontaneous burst potentials. In slices in which a su rgical cut isolated the CA1 and CA3 areas, thereby preventing the deve lopment of bursts in CA1, the effect on paired-pulse inhibition was le ssened but was still apparent. Adenosine deaminase, in the presence of (-)-bicuculline showed the same effect as cyclopentyltheophylline, de creasing substantially the amount of paired-pulse inhibition. These re sults suggest that adenosine may contribute to homosynaptic paired-pul se inhibition in disinhibited slices. For comparison, we also examined the effect of cyclopentyltheophylline in normal ((-)-bicuculline-free ) slices. At 100 nM, cyclopentyltheophylline increased reversibly the size of orthodromically evoked synaptic population potentials in the C A1 region of the slices and also reduced reversibly the degree of homo synaptic paired-pulse inhibition between two stimuli delivered only 30 ms apart. This suggests that adenosine may also contribute to shorter latency paired-pulse inhibition in the normal hippocampal slice.