To explore the neural damage induced by acute exposure to methamphetamine (METH).

The mice were administrated with METH, then the stereotyped behavior of mice was evaluated, and spatial recognition memory was analyzed by Y-maze test. In addition, nitric oxide synthase (NOS) activity was detected by kit, and the apoptotic proteins including Bax, Bcl-2, Caspase-3 were assayed by using Western blot. The DNA injury induced by METH was observed by using the comet assay. Moreover, mitochondrial membrane potential was detected to assess the toxic effects of METH on mitochondria by JC-1. With the Western blot assay, the phosphorylation of MAPK signaling pathways were also investigated.

Acute METH exposure significantly increased the stereotyped behavior in mice, and spatial recognition ability of mice was obviously decreased. On the molecular level, total nitric oxide synthase (TNOS) and induced nitric oxide synthase (iNOS) were increased, and the apoptotic proteins, such as Bax and cleaved caspase-3 were markedly enhanced. With the comet assay, it showed that METH exposure resulted in DNA damage. In parallel, mitochondrial membrane was damaged which manifested as mitochondrial membrane potential decreased. With the western blot, It was further found that METH enhanced the activation of MAPKs. However, p38 MAPK signaling pathway was demonstrated to be the only one factor involved in METH-induced neural damage.

METH induced neural damage, and MAPK signaling pathways might be involved in this process, since inhibition of p38 MAPK signaling pathway significantly ameliorated METH-induced neural damage.

Methamphetamine; Neural damage; MAPK signaling pathway