Ethanol-induced changes in synaptic amino acid neurotransmitter levels in the nucleus accumbens of differentially sensitized mice

  • Mina G. NashedEmail author
  • Dipashree Chatterjee
  • Diana Nguyen
  • Daria Oleinichenko
  • Mustansir Diwan
  • Jose N. Nobrega
Original Investigation



Ethanol-induced behavioural sensitization (EBS) does not occur uniformly in mice exposed to the sensitization paradigm. This suggests innate differential responses to ethanol (EtOH) in the reward circuitry of individual animals.


To better characterize the adaptive differences between low-sensitized (LS) and high-sensitized (HS) mice, we examined excitatory amino acid (EAA) and inhibitory amino acid (IAA) neurotransmitter levels in the nucleus accumbens (NAc) during EBS expression.


Male DBA/2J mice received five ethanol (EtOH) (2.2 g/kg) or saline injections, and locomotor activity (LMA) was assessed during EBS induction. EtOH mice were classified as LS or HS on the basis of final LMA scores. Following an EtOH challenge (1.8 g/kg) 2 weeks later, LMA was re-evaluated and in vivo microdialysis samples were collected from the NAc.


Most differences in amino acid levels were observed within the first 20 min after EtOH challenge. LS mice exhibited similar glutamate levels compared with acutely treated (previously EtOH naïve) mice, and generally increased levels of the IAAs GABA, glycine, and taurine. By contrast, HS mice exhibited increased glutamate and attenuated levels of GABA, glycine, and taurine.


These data suggest that the profile of amino acid neurotransmitters in the NAc of LS and HS mice significantly differs. Elucidating these adaptive differences contributes to our understanding of factors that confer susceptibility/resilience to alcohol use disorder.


Ethanol Neurotransmitter Nucleus accumbens Alcohol Amino acid Behavioural sensitization Glutamate GABA Glycine Taurine 



The authors thank Dr. Christina Nona and Roger Raymond for excellent technical assistance.

Funding information

This study was supported by NSERC grant RGPIN 06615.

Compliance with ethical standards

All procedures were approved by the Animal Care Committee at the Centre for Addiction and Mental Health and were in accordance with the guidelines and practices outlined by the Canadian Council on Animal Care.

Conflicts of interest

The authors declare that they have no conflicts of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Behavioural Neurobiology Laboratory, Research Imaging CentreCentre for Addiction and Mental HealthTorontoCanada
  2. 2.Departments of PsychologyUniversity of TorontoTorontoCanada
  3. 3.Departments of PsychiatryUniversity of TorontoTorontoCanada
  4. 4.Department of Pharmacology and ToxicologyUniversity of TorontoTorontoCanada
  5. 5.Campbell Family Mental Health Research InstituteCentre for Addiction and Mental HealthTorontoCanada

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