Hassan S F, Zumut S, Burke P G, McMullan S, Cornish J L, Goodchild A K
The Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
Neuropharmacology Laboratory, Department of Psychology, Macquarie University, NSW 2109, Australia.
Neuroscience. 2015 Jun 4;295:209-20. doi: 10.1016/j.neuroscience.2015.03.028. Epub 2015 Mar 23.
Methamphetamine (METH) is a psychostimulant that disrupts monoaminergic neurotransmission to evoke profound behavioral and physiological effects. Rapidly distributing to forebrain regions to increase synaptic concentrations of three monoamines (dopamine (DA), serotonin (5-HT) and noradrenaline (NA)), the medial prefrontal cortex (mPFC) is important in METH-altered behavioral and psychological profiles. Activation of the ventral mPFC can modify physiological variables, however, METH-evoked autonomic changes from this region are unknown. Therefore, the aim of this study was to characterize the respiratory, metabolic and cardiovascular effects of microinjection of METH, DA, 5-HT and NA into the ventral mPFC in urethane-anesthetized Sprague-Dawley rats. METH and NA microinjection evoked dose-related increases in heart rate, interscapular brown adipose tissue temperature and expired CO2, a pattern of response characteristic of non-shivering thermogenesis. NA and 5-HT microinjection elicited pressor and depressor responses, respectively, with matching baroreflex adjustments in sympathetic nerve activity while METH and DA evoked no change in vasomotor outflow. Low doses of METH and DA may evoke respiratory depression. These data suggest that METH's actions in the ventral mPFC, likely via adrenergic receptors, evoke non-shivering thermogenesis which may contribute to the increased body temperature and tachycardia seen in those that abuse METH.
甲基苯丙胺（METH）是一种精神兴奋剂，它会破坏单胺能神经传递，从而引发深刻的行为和生理效应。内侧前额叶皮质（mPFC）能迅速分布到前脑区域，以增加三种单胺（多巴胺（DA）、5-羟色胺（5-HT）和去甲肾上腺素（NA））的突触浓度，在METH改变的行为和心理特征中起重要作用。腹侧mPFC的激活可以改变生理变量，然而，METH从该区域引发的自主神经变化尚不清楚。因此，本研究的目的是描述在乌拉坦麻醉的Sprague-Dawley大鼠中，向腹侧mPFC微量注射METH、DA、5-HT和NA对呼吸、代谢和心血管的影响。微量注射METH和NA会引起心率、肩胛间棕色脂肪组织温度和呼出二氧化碳的剂量相关增加，这是一种非寒战产热的典型反应模式。微量注射NA和5-HT分别引起升压和降压反应，同时交感神经活动有匹配的压力反射调节，而METH和DA对血管运动流出没有影响。低剂量的METH和DA可能会引起呼吸抑制。这些数据表明，METH在腹侧mPFC的作用可能通过肾上腺素能受体引发非寒战产热，这可能导致滥用METH者出现体温升高和心动过速。
