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

PLoS One. 2015 Apr 30;10(4):e0125567. doi: 10.1371/journal.pone.0125567. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Glutamic Acid / metabolism*
  • Male
  • Microelectrodes*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology*
  • Rats
  • Synaptic Transmission / drug effects*


  • Ethanol
  • Glutamic Acid

Grant support

Support was provided by: Alcohol Research Council of the Swedish Alcohol Retailing Monopoly (Centralförbundet för alkohol och narkotikaupplysning CAN-SRA) [www.can.se]; H. Lundbeck A/S: lent us the glutamate recording unit. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.