Neuropharmacological modulation of the P3-like event-related potential in a rat two-tone auditory discrimination task with modafinil and NS9283, a positive allosteric modulator of α4β2 nAChRs

Neuropharmacology
Morten GrupeJesper Frank Bastlund

Abstract

The P300 (P3) event-related potential (ERP) is a neurophysiological signal believed to reflect cognitive processing of salient cues, and is thus used as a measure of attention and working memory. Additionally, P3 amplitude and latency is altered in neurological diseases and can be pharmacologically modulated. As P3-like ERPs can be recorded in rodents, it may serve as a potential translational biomarker of value for drug discovery. Here we investigated whether a positive allosteric modulator of α4β2 nicotinic acetylcholine receptors, NS9283, and the psychostimulant modafinil could modulate P3-like ERPs in healthy adult rats performing an auditory oddball discrimination task. ERPs were recorded with electroencephalography electrodes implanted into mediodorsal (MD) thalamus, medial prefrontal cortex, hippocampus and auditory cortex (AC). P3-like ERPs were detected in all brain regions, displaying larger amplitudes in target trials compared to non-target trials. Administration of modafinil (64 mg/kg) decreased P3-like ERP latency in MD thalamus and AC, whereas NS9283 augmented P3-like ERP amplitude in MD thalamus at 0.3 mg/kg and in AC at 3.0 mg/kg. Additionally, N1 pre-attention peak amplitude in MD thalamus was increased with 0....Continue Reading

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Citations

Apr 1, 2015·European Journal of Pharmacology·Arjan BloklandAnke Sambeth
Aug 2, 2015·Biochemical Pharmacology·Alvin V TerryCaterina M Hernandez
Apr 1, 2015·Annals of the New York Academy of Sciences·Robert E FeatherstoneSteven J Siegel
Feb 16, 2017·British Journal of Pharmacology·Jingyi Wang, Jon Lindstrom
Apr 15, 2015·The Journal of Biological Chemistry·Jingyi WangJon Lindstrom
Jun 8, 2018·Frontiers in Neural Circuits·Lezio S Bueno-Junior, Joao P Leite

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