Advances in molecular biology, including the creation of genetically altered mice, have had a tremendous impact on addiction research. Many mouse strains show altered responsiveness to cocaine and other abused drugs, providing a source of information on initial sites of action and downstream contributors to the effects of drugs. A powerful biosensor technique, fast-scan cyclic voltammetry (voltammetry), has recently been applied to the measurement of dopamine (DA) and other monoamine neurotransmitters in freely moving rats, and we propose to establish this technique for use in freely moving mice. This will allow monitoring of DA in mice with intact brain circuitry without the interference of anesthesia. In addition, the newest, state-of-the-art types of voltammetric recordings are of spontaneous DA release without any electrical stimulation. These measurements are true reflections of DA system activity that will be immensely helpful in determining how DA function is altered by cocaine and other abused drugs. DA "spikes", or rapid fluctuations of DA, are thought to be due to synchronous firing of DA neurons and provide a less artificial way of examining DA system activity than using electrical stimulation. The focus of this application is on two technical innovations: 1) use of voltammetry in freely moving mice and 2) recording spontaneous DA spikes. There are many applications of these measurements to addiction research in the future, including, for example, monitoring other neurotransmitters and using genetically altered or recombinant inbred mouse strains.

R21DA018815

2004-09-25

2007-07-31