Orexinergic neurotransmission in temperature responses to methamphetamine and stress: Mathematical modeling as a data assimilation approach

Abolhassan Behrouzvaziri, Daniel Fu, Patrick Tan, Yeonjoo Yoo, Maria V. Zaretskaia, Daniel Rusyniak, Yaroslav I. Molkov, Dmitry Zaretsky

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Experimental Data: Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult. Mathematical Modeling: We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods.

Original languageEnglish
Article numbere0126719
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 20 2015

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Methamphetamine
Synaptic Transmission
assimilation (physiology)
mathematical models
Temperature
dosage
temperature
Statistical methods
Orexin Receptors
Chemical activation
statistical analysis
receptors
Rats
Theoretical Models
processing technology
Mathematical models
antagonists
stress response
Injections
pretreatment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Orexinergic neurotransmission in temperature responses to methamphetamine and stress : Mathematical modeling as a data assimilation approach. / Behrouzvaziri, Abolhassan; Fu, Daniel; Tan, Patrick; Yoo, Yeonjoo; Zaretskaia, Maria V.; Rusyniak, Daniel; Molkov, Yaroslav I.; Zaretsky, Dmitry.

In: PLoS One, Vol. 10, No. 5, e0126719, 20.05.2015.

Research output: Contribution to journalArticle

Behrouzvaziri, Abolhassan ; Fu, Daniel ; Tan, Patrick ; Yoo, Yeonjoo ; Zaretskaia, Maria V. ; Rusyniak, Daniel ; Molkov, Yaroslav I. ; Zaretsky, Dmitry. / Orexinergic neurotransmission in temperature responses to methamphetamine and stress : Mathematical modeling as a data assimilation approach. In: PLoS One. 2015 ; Vol. 10, No. 5.
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