Measurements of the rewarding or discriminative stimulus effects, and sensitization to locomotor activity induced by abused drugs give us an available information for understanding of abuse liability and mechanism of abused drugs. Furthermore, genetic factors are known to play a role in the likelihood of drug abuse by humans. Psychostimulants, such as methamphetamine and cocaine, induce robust discriminative stimulus effects mediated through an activation of dopaminergic system without induction of the rewarding effects in Fischer 344 rats, unlike in the case of Lewis rats indicating gene expressions in the medium spiny neurons (MSN) could be determinants to establish the rewarding effects induced by psychostimulants in spite dopaminergic systems and sensing to the discriminative stimulus are properly worked. There are two types of MSNs (e.g., D₁- and D₂-receptor containing MSN, so called D₁-MSN and D₂-MSN) in the basal ganglia. Repeated administration of methamphetamine produced a sensitization to locomotor activity in mice. We found that the A_2A-receptor antagonist and d-opioid receptor agonist, which directly influence the D₂-MSN, but not D₁-receptor agonist, cross-sensitized to locomotor activity in methamphetamine sensitized mice. Since activation D₁-receptpr plays core role in the addictive behaviors themselves, our findings indicate that regulation of D₂-MSN play the regulatory role in the expression of such behaviors. Thus, regulations of MSNs are taking a part to express several addictive behaviors.