Different drug-susceptibilities of long-term potentiation in three input systems to the CA3 region of the guinea pig hippocampus in vitro.

The susceptibilities to several drugs of long-term potentiations in the three input systems (mossy, commissural/associational and fimbrial fibres) to CA3 pyramidal neurones were investigated in hippocampal slices from the guinea pig. D-2-Amino-5-phosphonovalerate (D-APV), a selective antagonist at N-methyl-D-aspartate (NMDA) receptors, blocked the long-term potentiations in the commissural/associational fibre- and fimbrial fibre-CA3 systems, but did not significantly affect that in the mossy fibre-CA3 system. The latter was suppressed by kynurenate, a non-selective glutamate receptor antagonist. On the other hand, naloxone, an opioid antagonist, inhibited and bifemelane, which improves metabolism in brain and has an anti-amnesic action, augmented long-term potentiation in mossy fibre-CA3 system but did not influence those in commissural/associational fibre- and fimbrial fibre-CA3 systems. These findings suggest that the mechanisms, relevant to production of long-term potentiation in the mossy fibre-CA3 system, are different from those in the commissural/associational fibre- and fimbrial fibre-CA3 systems. N-Methyl-D-aspartate receptors are involved in the latter systems, while non-NMDA receptors for L-glutamate and opioid receptors are involved in the former. Further, the mossy fibre-CA3 system is more susceptible to a drug, having an anti-amnesic action, than are the other two systems.