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.
Matsuoka
N
N
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Yamaguchi
I
I
Satoh
M
M
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003543:Cysteamine / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D002395:Catecholamines; D003543:Cysteamine; D008694:Methamphetamine; D010830:Physostigmine; D010879:Piperazines; D012601:Scopolamine; D013004:Somatostatin; D013449:Sulfonamides; C077882:FR 121196; D000096926:Benzenesulfonamides