Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer.

N-(4-Acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide (FR121196), a newly introduced putative cognitive enhancer of a derivative of piperazine, was investigated for its effects on long-term potentiation in guinea-pig hippocampal slices. The magnitude of long-term potentiation of population spikes recorded in CA3 pyramidal neurons was significantly augmented by perfusing FR121196 (10(-9)-10(-6) M) for 25 min before and during tetanic stimulation of the mossy fibers; the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10(-7) M. Similar activity and bell-shaped dose-response curve were observed with methamphetamine (10(-8)-10(-6) M). Physostigmine (10(-8)-10(-6) M) also facilitated long-term potentiation of this pathway and the magnitude of augmentation was concentration-dependent. Scopolamine (10(-6) M) per se had little effect on the magnitude of long-term potentiation in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FR121196 (10(-7) M) and physostigmine (10(-6) M), although it failed to influence that by methamphetamine (10(-7) M). In hippocampal slices from animals treated with cysteamine, which was shown to deplete hippocampal somatostatin, FR121196 (10(-7) M) hardly affected long-term potentiation generation, whereas physostigmine (10(-6) M) and methamphetamine (10(-7) M) augmented it significantly. These results suggest that FR121196 enhances the development of long-term potentiation in the mossy fiber-CA3 pathway through activation of somatostatinergic neurons in the hippocampal formation.