Behrouzvaziri Abolhassan, Zaretskaia Maria V, Rusyniak Daniel E, Zaretsky Dmitry V, Molkov Yaroslav I
Department of Mathematical Sciences, Indiana University Purdue University , Indianapolis, Indiana.
Department of Emergency Medicine, Indiana University School of Medicine , Indianapolis, Indiana.
Am J Physiol Regul Integr Comp Physiol. 2018 Jan 1;314(1):R43-R48. doi: 10.1152/ajpregu.00170.2017. Epub 2017 Sep 6.
Vital parameters of living organisms exhibit circadian rhythmicity. Although rats are nocturnal animals, most of the studies involving rats are performed during the day. The objective of this study was to examine the circadian variability of the body temperature responses to methamphetamine. Body temperature was recorded in male Sprague-Dawley rats that received intraperitoneal injections of methamphetamine (Meth, 1 or 5 mg/kg) or saline at 10 AM or at 10 PM. The baseline body temperature at night was 0.8°C higher than during the day. Both during the day and at night, 1 mg/kg of Meth induced monophasic hyperthermia. However, the maximal temperature increase at night was 50% smaller than during the daytime. Injection of 5 mg/kg of Meth during the daytime caused a delayed hyperthermic response. In contrast, the same dose at night produced responses with a tendency toward a decrease of body temperature. Using mathematical modeling, we previously showed that the complex dose dependence of the daytime temperature responses to Meth results from an interplay between inhibitory and excitatory drives. In this study, using our model, we explain the suppression of the hyperthermia in response to Meth at night. First, we found that the baseline activity of the excitatory drive is greater at night. It appears partially saturated and thus is additionally activated by Meth to a lesser extent. Therefore, the excitatory component causes less hyperthermia or becomes overpowered by the inhibitory drive in response to the higher dose. Second, at night the injection of Meth results in reduction of the equilibrium body temperature, leading to gradual cooling counteracting hyperthermia.
生物体的生命体征呈现昼夜节律性。尽管大鼠是夜行性动物，但大多数涉及大鼠的研究都是在白天进行的。本研究的目的是检测体温对甲基苯丙胺反应的昼夜变异性。在上午10点或晚上10点给雄性斯普拉格-道利大鼠腹腔注射甲基苯丙胺（Meth，1或5mg/kg）或生理盐水后，记录其体温。夜间的基础体温比白天高0.8°C。白天和夜间，1mg/kg的Meth均引起单相体温过高。然而，夜间的最大体温升高比白天小50%。白天注射5mg/kg的Meth会引起延迟的体温过高反应。相反，夜间注射相同剂量则会引起体温有下降趋势的反应。我们之前通过数学建模表明，白天体温对Meth反应的复杂剂量依赖性源于抑制性和兴奋性驱动之间的相互作用。在本研究中，我们使用我们的模型解释了夜间对Meth反应时体温过高的抑制现象。首先，我们发现夜间兴奋性驱动的基础活性更高。它似乎部分饱和，因此被Meth进一步激活的程度较小。因此，兴奋性成分引起的体温过高较少，或者在高剂量时被抑制性驱动所压倒。其次，夜间注射Meth会导致平衡体温降低，从而导致逐渐降温，抵消体温过高。
