title: Orexinergic neurotransmission in temperature responses to methamphetamine and stress: mathematical modeling as a data assimilation approach.
abstract: METHODS
  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.
  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.
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States of America.
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Behrouzvaziri
authors.affiliation: Park Tudor School, Indianapolis, IN 46240, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fu
authors.affiliation: Carmel High School, Carmel, IN 46032, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States of America.
authors.forename: Yeonjoo
authors.initials: Y
authors.lastname: Yoo
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Zaretskaia
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Rusyniak
authors.affiliation: Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, United States of America.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Zaretsky
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006979:Hyperthermia, Induced; D008297:Male; D008694:Methamphetamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D008959:Models, Neurological; D009010:Monte Carlo Method; D009287:Naphthyridines; D009434:Neural Pathways / Q000187:drug effects; D064446:Orexin Receptors / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013696:Temperature; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D064446:Orexin Receptors; D008694:Methamphetamine; D014508:Urea