This study investigates the involvement of α2-adrenergic receptors (AR) in mouse brain induced by a low dose of methamphetamine (METH, 2 mg/kg). Immunohistochemical studies show that α2A-AR increased in the dentate gyrus area of the hippocampus 24 h after five repeated administrations of METH. The hippocampal α2A-AR proteins rose 3.2-fold when compared to the saline-administered mice. The other adrenergic receptor, α1D-AR, were not changed by the treatment. Moreover, αo-subunits of GTP-binding proteins (Gαo), one of the downstream molecules of α2A-AR, was also increased by the treatment. These suggest that the repeated administration of low-doses of METH causes quantitative changes of the signaling of α2A-AR in the mouse hippocampus.