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School of Science Institute for
Mathematical Modeling and
Computational Science

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Modeling Effects of Amphetamines on Neural Control of Temperature 

PIs: Y. Molkov (Department of Mathematical Sciences, IUPUI), D. Zaretsky (Department of Emergency Medicine, IUSM)
Derivatives of amphetamines are widely abused all over the world. After long-term use they lead to cognitive, neurophysiological, and neuroanatomical deficits. Neurophysiological deficits are enhanced by hyperthermia, which itself is a major mortality factor in drug abusers. Temperature responses to injections of methamphetamine are multiphasic and include both hypothermic and hyperthermic phases, which are highly dependent on ambient temperature and previous exposure to the drug. Also, various derivatives directly affect various neuromediator systems, such as dopaminergic, noradrenergic, serotonergic. Finally, body temperature is dependent on multiple thermoregulatory mechanisms and complex neuronal circuitry. Not surprising that studying effects of amphetamines is very difficult due to multiplicity of factors involved. Most of research is focused on simplified experimental settings which do not have any predictability on real-life situations. We consider modeling as a breakthrough tool to design studies of translational value.
The long term goal of our project is to construct a comprehensive and physiologically relevant model of doze-dependent temperature response to methamphetamine representing interconnected neural structures which are experimentally proven to be specific brain areas and cell groups. We will start with generating a pilot set of experimental data on effect of inhibition of neuronal activity in the dorsomedial hypothalamus of the rat on temperature responses to a single dose of methamphetamine. Combining our existing pilot data and the data obtained in this project we will prepare an application for investigator-initiated grant of R01 type from National Institute of Drug Abuse, NIH.