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

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 microV. It was prolonged in both the cortex (Pz) and hippocampus by SC injection of 10 microg/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.

Visual event-related potencial (P300): a normative study

“…Common neuro-degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis often increase P300 latency. Moreover, studies have reported that some pharmaceuticals affect the latency of ERP's 21 . These substances may directly affect the transmission speed of neurons or the subject's alertness and, thus, affect component values 22,23 .…”

Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications

“…The P300 and P3-like AEP amplitude has been proposed to represent allocation of attentional resources and memory processing [132]. In monkeys, scopolamine prolonged the latency of the late P300-like potentials in the cortex and hippocampus, whereas the novel benzodiazepine inverse agonist S-8510 reversed the scopolamine-induced deficit [133]. Rats performing an active discriminant task displayed larger amplitudes in target trials compared to nontarget trials [134,135,136], and repeated methamphetamine administration in this model reduced the amplitude of P3-like AEP, indicating that changes in catecholamine transmission may affect the P3 generation [136], whereas modafinil, a drug used for improving alertness, lowered behavioral performance, decreased P3-like latency, and slightly affected its amplitude [134].…”

Queuing Network Modeling of a Real-Time Psychophysiological Index of Mental Workload—P300 in Event-Related Potential (ERP)

“…The current modeling approach has its limitations because it is the first step to quantify P300 amplitude and latency in dual-task situations using the queuing network modeling methods. Research has shown that other substances, e.g., acetylcholine, may also affect P300 amplitude [85], [86]; therefore, the current model-using NE to quantify P300 amplitude-is only one of the possible approaches to quantify P300 amplitude in dual tasks. Moreover, unlike some other modeling approaches (e.g., Micro-SAINT and IMPRINT) which have validated their prediction in many real systems and different task settings, the current modeling approach has not validated all of the predictions of the model (e.g., the prediction that a change of task difficulty level may not affect the P300 amplitude).…”