Molecular hydrogen attenuates methamphetamine-induced behavioral sensitization and activation of ERK-ΔFosB signaling in the mouse nucleus accumbens

Bin Cong, Bing Xie, Chunling Ma, Di Wen, Feng Yu, Jian Wang, Rongji Hui, Xi Shen, Yi Liu, Yixiao Luo

Read more:

DOI: 10.1016/j.pnpbp.2019.109781 DOI is the universal ID for this study.

This link will take you to the full study.


Methamphetamine (METH) is one of the most prevalently used illegal psychostimulants in many countries. Continuous exposure to METH leads to behavioral sensitization in animals, which can be used as a behavioral model with many mechanisms in common with relapse in humans. Molecular hydrogen has recently gained attention for its potential as a novel healthcare product with preventive and therapeutic applicability to a wide range of pathological conditions. However, it remains unclear whether and, if so, how hydrogen regulates METH-induced behavioral abnormalities. In the present study, we investigated the roles of molecular hydrogen on the acquisition and transfer of METH-induced behavioral sensitization and the accompanying changes in ERK phosphorylation and ΔFosB activation in the nucleus accumbens (NAc) of mice. To this end, male C57BL/6 mice received METH (0.1, 0.5 and 1.0 mg/kg, i.p.) injections for 7 days followed by a METH challenge (0.1, 0.5 and 1.0 mg/kg, i.p.) after a 7-day transfer period. Molecular hydrogen, delivered through a hydrogen-rich saline (HRS) injection (10 mL/kg, i.p., 3-h interval), was administered during the acquisition and transfer periods. We found that HRS administration was able to inhibit the acquisition and transfer of 0.1 and 0.5 mg/kg METH-induced behavioral sensitization to a certain extent, thereby attenuating the expression of behavioral sensitization. The HRS injections alone did not induce any obvious changes in locomotor activity in mice. Intriguingly, the increases in pERK and ΔFosB in the NAc, which accompanied the METH-induced behavioral sensitization, were also attenuated by the HRS treatments. Due to the anti-oxidative function of molecular hydrogen, the HRS injections reduced METH-induced reactive oxygen species and malondialdehyde generation in the NAc. These results suggest that molecular hydrogen serves as an anti-oxidative agent with potentially therapeutic applicability to the treatment of METH addicts.

Publish Year 2020
Country China
Rank Positive
Journal Progress in Neuropsychopharmacology and Biological Psychiatry
Primary Topic Brain
Secondary TopicAddiction
Model Mouse
Tertiary TopicDrug Toxicity (Methamphetamine)
Vehicle Saline (Dissolved)
pH Neutral
Application Injection