The capability to record neurotransmitter release in totally unrestrained animals to study the effects of drugs of abuse in prenatal animals, rat adolescent models of drug abuse and transgenic mice, has been limited, or even unattainable. We propose to develop a technology we call Neurochem Chip. This technology involves the development of microsensors that are capable of nearly specifically measuring neurochemicals such as glutamate and GABA, using photolithographically designed microelectrodes and a self-referencing recording approach. In this Stage 1 proposal, Neurochem Chips will be integrated to polyimide flex cables in order to carry out recordings of neurotransmitter release in the frontal cortex, striatum and hippocampus in tethered, awake behaving rats. Pilot studies and prior work support that Neurochem Chip can reliably measure L-glutamate using a self-referencing recording paradigm. However, refinements in technology are needed in order to carry out such recordings in the awake behaving animal to lay the foundation for the development of a totally untethered recording system involving telemetry technology. In addition, a new prototype sensor that will allow for the simultaneous measures of both glutamate and GABA will be investigated. In Stage 2, the recording circuitry will be miniaturized and a total telemetric system will be developed so that large numbers of rats and mice can be recorded. In general, these technologies will allow for the rapid screening of the effects of drugs of abuse on brain neurotransmitter systems, acutely and chronically, in both adult and developing rats and mice which cannot be carried out using current technology. In addition, Neurochem Chip can possibly be developed to measure a large number of other neurotransmitters.
