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

Abstract
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.
AuthorsN Matsuoka, I Yamaguchi, M Satoh
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 241 Issue 1 Pg. 27-34 (Sep 07 1993) ISSN: 0014-2999 [Print] Netherlands
PMID7901036 (Publication Type: Journal Article)
Chemical References
  • Catecholamines
  • Piperazines
  • Sulfonamides
  • FR 121196
  • Methamphetamine
  • Somatostatin
  • Cysteamine
  • Physostigmine
  • Scopolamine
Topics
  • Animals
  • Catecholamines (metabolism)
  • Cognition (drug effects)
  • Cysteamine (pharmacology)
  • Electrophysiology
  • Guinea Pigs
  • Hippocampus (drug effects, metabolism)
  • In Vitro Techniques
  • Long-Term Potentiation (drug effects)
  • Male
  • Methamphetamine (pharmacology)
  • Nerve Fibers (drug effects)
  • Neural Pathways (drug effects)
  • Physostigmine (pharmacology)
  • Piperazines (pharmacology)
  • Scopolamine (pharmacology)
  • Somatostatin (metabolism, physiology)
  • Sulfonamides (pharmacology)

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