Serotonin plays a vital role in controlling mood, anxiety states and reward-related behaviors via its actions in the central nervous system. We are investigating the use of in vivo fast cyclic voltammetry with 5 μm × 80 μm cylindrical carbon fiber microelectrodes to study changes in serotonin transmission (reuptake and release rates) in the hippocampus and frontal cortex in response to constitutive reductions in SERT compared to chronic serotonin reuptake inhibitor administration. Both are hypothesized to eliminate/decrease serotonin reuptake, however, they ultimately have different effects on anxiety-related phenotypes. In addition, serotonergic firing rates have been shown to be greatly decreased inSERT deficient mice (Gobbi, et al., 2001) and this differs from the return to normal firing rates hypothesized to occur following chronic antidepressant treatment. We have implemented isoflurane anesthesia and have had much greater success compared to a number of injectable anesthetic combinations in maintaining hours long surgical anesthetic planes and survival in mice. We are stimulating serotonin release directly from electrodes placed near the raphe nuclei and monitoring the release and reuptake of serotonin in the hippocampus and frontal cortex. We routinely observe linear responses to serotonin at carbon fiber electrodes over a 50 nM - 5 μM concentration range. We are also exploring the use of boron-doped diamond (BDD) electrodes to monitor serotonin neurotransmission. BDD electrodes have been shown to have minimal fouling in the presence of high serotonin concentrations. Preliminary studies using a 40 μm diameter BDD electrode showed 100 nM limits of detection for serotonin with linear responses up to 10 μM. Using this type of electrode, we are able to distinguish between serotonin and norepinephrine oxidation peaks using fast cyclic voltammetry at 300 V/s. Since collateral stimulation of norepinephrine cell bodies in the locus coeruleus by stimulating electrodes placed near the raphe nuclei might occur, BDD electrodes could present advantages over carbon fiber electrodes beyond those already determined with respect to fouling.