The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride.

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.