EFFECT OF ADENOSINE ON BICUCULLINE-RESISTANT PAIRED-PULSE INHIBITION IN THE RAT HIPPOCAMPAL SLICE

This study extends previous investigations into the effect of adenosin e on bicuculline-resistant paired-pulse inhibition between field poten tials evoked 300 ms apart in the CA1 area of the rat hippocampal slice . A direct assessment of the effect of adenosine on paired-pulse inhib ition is complicated by the facts that adenosine directly depresses ev oked potentials and bicuculline-resistant paired-pulse inhibition is g reater between pairs of small potentials than between pairs of larger potentials. Adenosine increased bicuculline-resistant paired-pulse inh ibition when stimulus strength was constant between adenosine and cont rol but paired-pulse inhibition of responses in adenosine was markedly less than paired-pulse inhibition of control responses of the same si ze. Furthermore, adenosine decreased the size of conditioned potential s to a significantly lesser extent than unpaired potentials of the sam e initial size. Taken together the results indicate that adenosine can decrease bicuculline-resistant paired-pulse inhibition in the hippoca mpus. A possible mechanism for this effect is that adenosine is suppre ssing transmission at excitatory terminals onto interneurones which wo uld suggest that these receptors are more sensitive to adenosine than those on the Schaffer collateral/CA1 pyramidal cell synapses. In this case adenosine should reduce paired-pulse inhibition at lower concentr ations than are required for depression of single evoked potentials. A comparison of the concentration-response relationships for the effect s of adenosine on paired-pulse inhibition and on single evoked potenti als ruled out greater sensitivity of adenosine receptors at excitatory terminals onto interneurones as an explanation for adenosine's action on bicuculline-resistant paired-pulse inhibition. Adenosine was less effective at reducing inhibition evoked by large supramaximal conditio ning stimuli than by stimuli submaximal for evoked potential size, alt hough control paired-pulse inhibition is larger in the latter case. Th is finding is consistent with adenosine reducing bicuculline-resistant paired-pulse inhibition by causing an increase in simultaneous paired -pulse facilitation. (C) 1995 Wiley-Liss, Inc.