Resting glutamate levels and rapid glutamate transients in the prefrontal cortex of the Flinders Sensitive Line rat: a genetic rodent model of depression

Neuropsychopharmacology. 2011 Jul;36(8):1769-77. doi: 10.1038/npp.2011.60. Epub 2011 Apr 27.


Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (~30%) and slow onset of action (2-4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 × 333 μm) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3-5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Depression / genetics
  • Depression / metabolism*
  • Depression / psychology*
  • Disease Models, Animal*
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis / methods
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Mutant Strains
  • Rest / physiology*
  • Time Factors


  • Glutamic Acid