Effects of the GluN2B-selective antagonist Ro 63-1908 on acquisition and expression of methamphetamine conditioned place preference in male and female rats

GluN2B 选择性拮抗剂 Ro 63-1908 对雄性和雌性大鼠甲基苯丙胺条件性位置偏好习得和表达的影响

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作者:Justin R Yates, Hunter L Campbell, Lauren L Hawley, Matthew J Horchar, Joy L Kappesser, Makayla R Wright

Background

Methamphetamine abuse has increased significantly in recent years. Currently, there are no FDA-approved pharmacotherapies for the treatment of methamphetamine use disorder. The goal of the current study was to determine if the N-methyl-d-aspartate (NMDA) GluN2B-selective antagonist Ro 63-1908 can block the conditioned rewarding effects of methamphetamine as assessed in conditioned place preference (CPP).

Conclusions

The results of this study show that Ro 63-1908 is able to decrease the conditioned rewarding effects of methamphetamine.

Methods

Two main experiments were conducted. In the first experiment, male (n = 24) and female (n = 24) rats received either vehicle or Ro 63-1908 (1.0-10.0 mg/kg) 30 min prior to the posttest to determine if blocking the GluN2B subunit attenuates expression of methamphetamine CPP. In the second experiment, male (n = 18) and female (n = 18) rats received either vehicle or Ro 63-1908 (1.0 or 3.0 mg/kg) 30 min prior to each conditioning session to determine if blocking the GluN2B subunit attenuates acquisition of methamphetamine CPP.

Results

Ro 63-1908 (3.0 mg/kg) blocked acquisition of methamphetamine CPP in male rats, but only attenuated CPP in female rats. Ro 63-1908 did not alter expression of CPP in either sex. Increasing the dose of Ro 63-1908 (10.0 mg/kg) failed to block acquisition of CPP in an additional group of female rats (n = 6). A control experiment showed that Ro 63-1908 (3.0 mg/kg) did not produce CPP or conditioned place aversion in male rats (n = 6) or in female rats (n = 6). Conclusions: The results of this study show that Ro 63-1908 is able to decrease the conditioned rewarding effects of methamphetamine.

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