The applicants propose the development of a subcutaneously implantable microbolus infusion pump (MIP) for neuroscience research in small animals, where the research paradigms require conscious, behaving animals in a non-tethered state. The MIP will allow in vivo incremental dosing of drugs by remote activation, as well as sequential administration of different pharmacologic agents, via the external jugular vein. This capability will make the MIP a powerful tool for examining acute behavioral and physiologic effects of pharmacologic agents in animal models of human disease. Use of the MIP should allow investigations of the acute effects of pharmacologic agents on animal behaviors sensitive to interference by handling (e.g., mating, aggression, sleep, circadian rhythms). Furthermore, the MIP will allow noninvasive study of the acute effect of pharmacologic agents on physiologic parameters that are typically confounded by the effects of handling stress on the animal (e.g., stress hormones, cardiovascular parameters, brain electrical activity, temperature). Pilot data are provided which suggest that infusion of radiotracers with the MIP in the freely moving animal allows imaging of acute changes in regional blood flow associated with brain activation. Such functional neuroimaging of complex animal behaviors cannot be undertaken with the current technologies. In transgenic mice, the MIP promises to improve the characterization of the phenotypic effects of gene deletions/insertions. The 4 goals of this project are: (1) to optimize and develop the design of the MIP for rats, (2) to validate the ability of MIP to provide precise, remotely activated bolus infusion of a drug in freely behaving rats, without interfering with the normal behavior and physiological parameters, and allowing the generation of cerebral blood flow images, (3) to miniaturize the MIP for mice, and (4) to design and test a dual chamber MIP that allows independent, controlled release of two separate pharmacologic agents.
| Chen, Kevin; Holschneider, Daniel P; Wu, Weihua et al. (2004) A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem 279:39645-52 |
| Holschneider, D P; Scremin, O U; Chialvo, D R et al. (2002) Heart rate dynamics in monoamine oxidase-A- and -B-deficient mice. Am J Physiol Heart Circ Physiol 282:H1751-9 |
| Holschneider, D P; Scremin, O U; Roos, K P et al. (2002) Increased baroreceptor response in mice deficient in monoamine oxidase A and B. Am J Physiol Heart Circ Physiol 282:H964-72 |
| Maarek, J M; Holschneider, D P; Harimoto, J (2001) Fluorescence of indocyanine green in blood: intensity dependence on concentration and stabilization with sodium polyaspartate. J Photochem Photobiol B 65:157-64 |
| Holschneider, D P; Chen, K; Seif, I et al. (2001) Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B. Brain Res Bull 56:453-62 |
