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This study investigates the involvement of alpha2-adrenergic receptors (AR) in mouse brain induced by a low dose of methamphetamine (METH, 2 mg/kg). Immunohistochemical studies show that alpha2A-AR increased in the dentate gyrus area of the hippocampus 24 h after five repeated administrations of METH. The hippocampal alpha2A-AR proteins rose 3.2-fold when compared to the saline-administered mice. The other adrenergic receptor, alpha1D-AR, were not changed by the treatment. Moreover, alphao-subunits of GTP-binding proteins (Galphao), one of the downstream molecules of alpha2A-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 alpha2A-AR in the mouse hippocampus.