Noradrenergic antagonism of the P13 and N40 components of the rat auditory evoked potential

Abstract

Rationale: Two rat auditory evoked potential (AEP) components P13 and N40 are suggested as analogues to the human P50, which has abnormal suppression properties in schizophrenia. However, P50 likely reflects neural activity from several different brain areas. Studies examining each of these components in the rat model have proposed circuitry that involves alpha2 norepinephrine (NE) receptors, and different disruption effects are predicted depending on whether effects are presynaptic or postsynaptic.

Objectives: The aim of this paper is to test differential effects of NE antagonism on disruption of normal P13 and N40 expression.

Materials and methods: AEPs were recorded simultaneously in alert, freely moving rats using the alpha2 antagonist yohimbine. Amplitudes of P13 and N40 elicited by 500-ms interstimulus interval click pairs were measured after administration of a placebo and three doses of the yohimbine.

Results: A high dose of yohimbine yielded smaller P13 amplitudes to both clicks, consistent with presynaptic action. However, a moderate yohimbine dose yielded increased P13 amplitudes to both clicks. For N40, a moderate dose of yohimbine yielded increased amplitudes to the second stimulus, and a high dose restored normal suppression, which is consistent with previously reported findings.

Conclusions: This study demonstrated that noradrenergic activity differentially affects P13 and N40 components. As P13 and N40 are each models of human P50, these findings highlight the complex circuitry that likely underlies P50. An appreciation for these complexities is critical for understanding the mechanisms of the P50 suppression deficit in schizophrenia, which may be influenced by both trait and state factors.