Effects of S-8510, a benzodiazepine receptor partial inverse agonist, on event-related potentials (P300) in monkeys

Kohji Abe, Toru Sawada, Masahito Horiuchi, Kohji Yoshimura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The present study investigated the effects of a novel benzodiazepine inverse agonist, S-8510 [2-(3-isoxazolyl)-3, 6, 7, 9-tetrahydroimidazo [4, 5- d] pyrano [4,3-b] pyridine monophosphate monohydrate], on the P300 components of the event-related potential (ERP) in monkeys. Late positive potentials (P300-like potentials) from the cortex (Pz) and hippocampus recorded using the auditory oddball paradigm in combination with electrical reinforcement can be measured in rhesus monkeys. The latency of this P300-like potential recorded from the monkey cortex was 330 ms, and the amplitude was 13 μV. It was prolonged in both the cortex (Pz) and hippocampus by SC injection of 10 μg/kg scopolamine, a muscarinic receptor antagonist. Oral administration of S-8510 (3, 10 mg/kg) had no effect on the latency in normal monkeys. However, S-8510 reversed the scopolamine-induced prolongation of P300-like potentials on the cortex (Pz) and hippocampus. These results show that S-8510 can attenuate the effects induced by scopolamine on P300-like potentials associated with cognitive function in monkeys, suggesting that S-8510 may be useful as a therapeutic drug in disease-associated cognitive dysfunctions of the central nervous system.

Original languageEnglish
Pages (from-to)71-76
Number of pages6
JournalPsychopharmacology
Volume141
Issue number1
DOIs
Publication statusPublished - May 4 1999
Externally publishedYes

Keywords

  • Benzodiazepine inverse agonist
  • Event-related potential
  • P300-like potential
  • S-8510
  • Scopolamine

ASJC Scopus subject areas

  • Pharmacology

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