PT - JOURNAL ARTICLE AU - K. N. Hascup AU - E. R. Hascup AU - F. Pomerleau AU - P. Huettl AU - G. A. Gerhardt TI - Second-by-Second Measures of <span class="sc">l</span>-Glutamate in the Prefrontal Cortex and Striatum of Freely Moving Mice AID - 10.1124/jpet.107.131698 DP - 2008 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 725--731 VI - 324 IP - 2 4099 - http://jpet.aspetjournals.org/content/324/2/725.short 4100 - http://jpet.aspetjournals.org/content/324/2/725.full SO - J Pharmacol Exp Ther2008 Feb 01; 324 AB - l-Glutamate (Glu) is the main excitatory neurotransmitter in the mammalian central nervous system, and it is involved in most aspects of normal brain function, including cognition, memory and learning, plasticity, and motor movement. Although microdialysis techniques have been used to study Glu, the slow temporal resolution of the technique may be inadequate to properly examine tonic and phasic Glu. Thus, our laboratory has developed an enzyme-based microelectrode array (MEA) with fast response time and low detection limits for Glu. We have modified the MEA design to allow for reliable measures in the brain of awake, freely moving mice. In this study, we chronically implanted the MEA in prefrontal cortex (PFC) or striatum (Str) of awake, freely moving C57BL/6 mice. We successfully measured Glu levels 7 days postimplantation without loss of MEA sensitivity. In addition, we determined resting (tonic) Glu levels to be 3.3 μM in the PFC and 5.0 μM in the Str. Resting Glu levels were subjected to pharmacological manipulation with tetrodotoxin (TTX) and dl-threo-β-hydroxyaspartate (THA). TTX significantly (p &lt; 0.05) decreased resting Glu by 20%, whereas THA significantly (p &lt; 0.05) increased resting Glu by 60%. Taken together, our data show that chronic recordings of tonic and phasic clearance of exogenously applied Glu can be carried out in awake mice for at least 7 days in vivo, allowing for longer term studies of Glu regulation. The American Society for Pharmacology and Experimental Therapeutics