| The neurotransmitter dopamine has shown to be of central importance to difference brain functions, such as movement, reward, and addiction. A biosensor for the detection of dopamine in the brain should have a fast time response to monitor concentration changes which happen on a subsecond time scale. Furthermore, the sensor should have a high sensitivity to dopamine, because the physiological concentrations of dopamine were found to be in the range form nanomolar to lower micromolar. High selectivity is also necessary to distinguish the desired signal from electrochemical interferences in the brain such as ascorbic acid. Fast scan cyclic voltammetry at glass-encased carbon fiber microelectrodes has been shown to fulfill these requirements and is therefore often used for measurements of easily oxidizable neurotransmitters like dopamine. In this dissertation, some drawbacks of the technique and the sensor are addressed and improved.; Chapter 1 contains an overview of electrochemical methods that have been used to detect various neurotransmitters in the brain. Chapter 2 explains a method to increase the sensitivity and selectivity for dopamine of carbon fiber microelectrodes by covalent attachment of a cation-exchange layer to the electrode surface. A method utilizing tungsten microwires as substrate for the construction of flexible gold, platinum, and carbon microelectrodes is described in Chapter 3 and 4. Carbon-coated tungsten microwires have then been examined for use as in vivo dopamine sensor. The microwires showed the same electrochemical properties as conventional glass-encased carbon fiber microelectrodes. In chapters 5 and 6 a novel instrumental method to subtract of the large background current, which occurs during application of fast scan rates, is presented. This method has then been used to examine the changes in this background current and account for these changes. This enabled us to expand the time course for fast scan voltammetric measurements 20-fold. Furthermore, the origin of these background changes was examined. In the last chapter tungsten based microelectrodes were used to evaluate changes in dopamine concentrations and pH of the extracellular fluid in a primate brain during reward delivery. |
