Among voltage-gated Ca²⁺ channels (VGCCs), low VGCCs/T-type Ca²⁺ channels (T-channels) regulate neuronal excitation and spontaneous neurotransmitter release, while high VGCCs are essential for evoked neurotransmitter release. It is still largely open to question how VGCCs contribute to CNS actions of psychostimulants, such as amphetamine and methamphetamine (MA). Interestingly, it has been reported that genetic deletion of Ca_v3.2 T-channels reduces amphetamine-induced hyperlocomotion (HL) in mice. Here, we examined effects of a selective T-channel blocker, TTA-A2, on MA-induced HL and brain Fos expression in C57BL/6J mice, as compared to pregabalin, a high VGCC α2δ inhibitor. TTA-A2, administered i.p. at 1 mg/kg, strongly suppressed MA-induced HL. In contrast, i.p. pregabalin at 1, 10 or 30 mg/kg had no such effect, although it exhibited slight suppressive effect at 3 mg/kg. MA caused cFos expression in specific brain areas including the prefrontal cortex, striatum, paraventricular hypothalamic nucleus, and hippocampal dentate gyrus and CA3 region, which were almost abolished by TTA-A2. Together, T-channels appear to play a critical role in MA-induced neuronal and behavioral excitation in C57BL/6J mice.