Repetitive administration of aripiprazole enhances locomotor response to methamphetamine in mice

Dopamine receptor partial agonists have been proposed as potential candidate agents to treat psycho-stimulant abuse. Aripiprazole is a dopamine D2/D3 receptor partial agonist that is currently used as an antipsychotic drug in clinical settings. This study aimed to examine whether aripiprazole can suppress the methamphetamine-induced locomotor response in mice that is used as an indicator for potential clinical use. In ICR mice pre-exposed to methamphetamine (1. mg/kg subcutaneous injection once daily for 7 days), we found that mice receiving repetitive treatments with aripiprazole (1, 5, and 10. mg/kg, respectively; intraperitoneal injection once daily for 1 week) showed a significantly enhanced locomotor response upon re-exposure to methamphetamine (0.5. mg/kg), compared with animals that received a vehicle treatment. Furthermore, we found that methamphetamine-naïve mice receiving repetitive treatment with aripiprazole (5. mg/kg intraperitoneal injection once daily for 1 week) also showed a significantly enhanced locomotor response to acute challenge with methamphetamine (0.5. mg/kg), compared with animals receiving the vehicle treatment. The enhanced locomotor response to methamphetamine in both methamphetamine-pre-exposed and methamphetamine-naïve mice lasted at least four weeks in this study. Our data suggest that aripiprazole may enhance the effects of methamphetamine, so caution should be exercised when prescribing to individuals with histories of stimulant use.