# The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride.
> メタンフェタミン誘発うつ様行動における高体温の役割：コーラルカルシウムハイドライドの保護効果


## Abstract

Methamphetamine (METH) abuse inflicts irreversible harm on the central nervous system, producing psychiatric manifestations such as depression. This study examined the contribution of hyperthermia to METH-associated depression-like behaviors in mice exposed to either normal or elevated ambient temperatures. High ambient temperature was found to exacerbate METH-induced hyperthermia and was essential for the emergence of depression-like behaviors; chronic METH exposure under normal temperature alone did not produce these behaviors. High ambient temperature also worsened hippocampal synaptic plasticity impairment, oxidative stress responses, and neuroinflammation. Coral calcium hydride (CCH), a hydrogen-rich powder that releases hydrogen gas upon contact with water, was evaluated as an intervention. CCH pretreatment markedly reduced METH-induced hyperthermia, while post-exposure CCH administration suppressed depression-like behaviors and attenuated hippocampal synaptic plasticity damage. CCH also lowered lactate dehydrogenase activity and reduced hippocampal levels of malondialdehyde, TNF-α, and IL-6, indicating antioxidant and anti-inflammatory actions.

### Mechanism

CCH releases molecular hydrogen upon contact with water; the hydrogen scavenges reactive oxygen species, thereby reducing oxidative stress markers (MDA, LDH) and suppressing neuroinflammatory mediators (TNF-α, IL-6) to preserve hippocampal synaptic plasticity.

## Bibliographic

- **Authors**: Wang X, Tong B, Hui R, Hou C, Zhang Z, Zhang LL, et al.
- **Journal**: Front Mol Neurosci
- **Year**: 2021
- **PMID**: [35058751](https://pubmed.ncbi.nlm.nih.gov/35058751/)
- **DOI**: [10.3389/fnmol.2021.808807](https://doi.org/10.3389/fnmol.2021.808807)
- **PMC**: [PMC8764150](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764150/)
- **Study type**: animal study
- **Delivery route**: animal model
- **Effect reported**: positive

## Delivery context

This study is at the animal-experiment stage. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study is at the animal-experiment stage. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 35058751. https://h2-papers.org/en/papers/35058751
> **Source**: PubMed PMID [35058751](https://pubmed.ncbi.nlm.nih.gov/35058751/)