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.
