Involvement of dopamine D2 receptor in a single methamphetamine-induced behavioral sensitization in C57BL/6J mice

A single exposure to drugs of abuse is sufficient to induce behavioral sensitization, which is a form of long-lasting neuroplasticity. Dopamine D2 receptors are the main receptor for antipsychotic drugs, but little is known about their role in a single methamphetamine-induced behavioral sensitization. In the present study, we examined whether typical antipsychotic haloperidol and atypical antipsychotic risperidone, both targeting dopamine D2 receptor, could prevent the methamphetamine sensitization when they were given at the different phase of behavioral sensitization. A single methamphetamine exposure induced robust and reliable behavioral sensitization to the lower challenge dose of methamphetamine after 7 days of drug-free period. At doses that did not affect general locomotion, haloperidol and risperidone not only significantly attenuated methamphetamine induced hyperlocomotion, but also completely prevented the development of behavioral sensitization to methamphetamine challenge when they were pretreated before the first exposure to methamphetamine. When haloperidol and risperidone were given in the early period of transfer (2 h after the first methamphetamine exposure), they also dose-dependently attenuated the transfer to expression of methamphetamine sensitization from the hyperlocomotion. These data suggest that dopamine D2 receptors play an important role in methamphetamine sensitization, especially in protecting against the development and transfer in the earlier labile period after the methamphetamine exposure. Therefore, clinically approved dopamine D2 receptor antagonists may be useful in the treatment of methamphetamine addiction.