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This study was carried out to determine the roles of dopamine D1 and D2 receptors on the up-regulation of α(2)/δ subunit of voltage-gated Ca(2+) channels (VGCCs) induced by methamphetamine (METH). In the conditioned place preference paradigm, METH-induced place preference suppressed with gabapentin, an antagonist for α(2)/δ subunit. Under these conditions, the increase in α(2)/δ subunit expression was found in the frontal cortex and limbic forebrain. ⋯ The expression of α(2)/δ subunit protein and its mRNA was significantly enhanced in the METH-treated cortical neurons. These increases in protein and mRNA of α(2)/δ subunit were completely abolished by SCH23390 and sulpiride with simultaneous exposure to METH. These findings indicate that up-regulation of α(2)/δ subunit is regulated through the activation of dopamine D1 and D2 receptors during METH treatment.