The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride.
The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride.
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DOI：
10.3389/fnmol.2021.808807
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wen D
中科院分区：
文献类型：
--
作者：
Wang X;Tong B;Hui R;Hou C;Zhang Z;Zhang L;Xie B;Ni Z;Cong B;Ma C;Wen D
滥用甲基苯丙胺（METH）会对中枢神经系统造成不可逆转的损害，并导致包括抑郁症在内的精神症状。值得注意的是，冰毒引起的高热是这些症状发生的关键因素，因为它会加剧冰毒引起的神经毒性。然而，高温在冰毒引起的抑郁样行为中的作用需要澄清。在本研究中，我们在正常（NAT）或高环境温度（HAT）下用不同剂量的冰毒治疗小鼠。我们发现 HAT 在 METH 治疗后促进体温过高，并在 METH 诱导的小鼠抑郁样行为中发挥关键作用。有趣的是，长期接触冰毒（10 mg/kg，7 或 14 天）或在 NAT 下逐渐增加剂量（2 ∼ 15 mg/kg，3 天）冰毒并不能诱发抑郁样行为。然而，HAT 加剧了 METH 引起的海马突触可塑性损伤、氧化应激反应和神经炎症。分子氢作为一种抗氧化剂和抗炎剂，已被证明在多种疾病中具有预防和治疗的适用性。珊瑚氢化钙（CCH）是一种新发现的富氢粉末，当接触到水时会逐渐产生氢气。在此，我们发现CCH预处理显着减弱了METH引起的高热，并且METH暴露后给予CCH也抑制了METH引起的抑郁样行为并减少了海马突触可塑性损伤。此外，CCH有效降低乳酸脱氢酶的活性，减少海马中丙二醛、TNF-α和IL-6的生成。这些结果表明，CCH 是一种有效的富氢剂，在治疗冰毒滥用者方面具有潜在的治疗应用价值。
Methamphetamine (METH) abuse causes irreversible damage to the central nervous system and leads to psychiatric symptoms including depression. Notably, METH-induced hyperthermia is a crucial factor in the development of these symptoms, as it aggravates METH-induced neurotoxicity. However, the role of hyperthermia in METH-induced depression-like behaviors needs to be clarified. In the present study, we treated mice with different doses of METH under normal (NAT) or high ambient temperatures (HAT). We found that HAT promoted hyperthermia after METH treatment and played a key role in METH-induced depression-like behaviors in mice. Intriguingly, chronic METH exposure (10 mg/kg, 7 or 14 days) or administration of an escalating-dose (2 ∼ 15 mg/kg, 3 days) of METH under NAT failed to induce depression-like behaviors. However, HAT aggravated METH-induced damage of hippocampal synaptic plasticity, reaction to oxidative stress, and neuroinflammation. Molecular hydrogen acts as an antioxidant and anti-inflammatory agent and has been shown to have preventive and therapeutic applicability in a wide range of diseases. Coral calcium hydride (CCH) is a newly identified hydrogen-rich powder which produces hydrogen gas gradually when exposed to water. Herein, we found that CCH pretreatment significantly attenuated METH-induced hyperthermia, and administration of CCH after METH exposure also inhibited METH-induced depression-like behaviors and reduced the hippocampal synaptic plasticity damage. Moreover, CCH effectively reduced the activity of lactate dehydrogenase and decreased malondialdehyde, TNF-α and IL-6 generation in hippocampus. These results suggest that CCH is an efficient hydrogen-rich agent, which has a potential therapeutic applicability in the treatment of METH abusers.
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