Effects of age and acute ethanol on glutamatergic neurotransmission in the medial prefrontal cortex of freely moving rats using enzyme-based microelectrode amperometry.

Devesh Mishra,Nicholas R Harrison,Björn Schilström,Åsa Konradsson-Geuken,Carolina B Gonzales

doi:10.1371/journal.pone.0125567

Devesh Mishra, Nicholas R Harrison + Show 3 more

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https://doi.org/10.1371/journal.pone.0125567

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Journal: PloS one	Publication Date: Apr 30, 2015
Citations: 12	License type: CC BY 4.0

Affiliation: Karolinska Institutet, University of Gothenburg

Abstract

Ethanol abuse during adolescence may significantly alter development of the prefrontal cortex which continues to undergo structural remodeling into adulthood. Glutamatergic neurotransmission plays an important role during these brain maturation processes and is modulated by ethanol. In this study, we investigated glutamate dynamics in the medial prefrontal cortex of freely moving rats, using enzyme-based microelectrode amperometry. We analyzed the effects of an intraperitoneal ethanol injection (1 g/kg) on cortical glutamate levels in adolescent and adult rats. Notably, basal glutamate levels decreased with age and these levels were found to be significantly different between postnatal day (PND) 28-38 vs PND 44-55 (p<0.05) and PND 28-38 vs adult animals (p<0.001). We also observed spontaneous glutamate release (transients) throughout the recordings. The frequency of transients (per hour) was significantly higher in adolescent rats (PND 28-38 and PND 44-55) compared to those of adults. In adolescent rats, post-ethanol injection, the frequency of glutamate transients decreased within the first hour (p<0.05), it recovered slowly and in the third hour there was a significant rebound increase of the frequency (p<0.05). Our data demonstrate age-dependent differences in extracellular glutamate levels in the medial prefrontal cortex and suggest that acute ethanol injections have both inhibitory and excitatory effects in adolescent rats. These effects of ethanol on the prefrontal cortex may disturb its maturation and possibly limiting individuals´ control over addictive behaviors.

Highlights

Brain development and maturation continues during adolescence until adulthood in humans [1]
We know surprisingly little about glutamatergic neurotransmission in the prefrontal cortex during development and how it is affected by ethanol
We observed an age-dependent decrease in basal glutamate levels in the medial prefrontal cortex (mPFC) of rats

Summary

Introduction

Brain development and maturation continues during adolescence until adulthood in humans [1]. Excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors play a critical role in processes involved in synapse strengthening or removal [4,5,6,7]. The excitatory neurotransmitter glutamate, activating the NMDA receptor, likely plays an important role in normal brain development. Ethanol consumption during adolescence has been suggested to interfere with maturational processes and can have detrimental effects on overall brain development. Ethanol has been shown to inhibit firing activity of neurons in the prefrontal cortex, an effect that could be mimicked by the NMDA receptor antagonist APV [11]. Using electrophysiological recordings in slice preparations from pre-adolescent animals, acute exposure to ethanol has been shown to inhibit NMDA receptor-mediated excitatory postsynaptic currents in the deep layer pyramidal neurons of the prefrontal cortex, suggesting no effect on glutamate release [12]. Exert an inhibitory effect on glutamatergic neurotransmission mainly via blockade of postsynaptic NMDA receptors

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