Repeated adenosine pre-treatment potentiates the acute effect of methamphetamine in rats

Adenosine was intraperitoneally (i.p.) injected to Wistar rats every 3 days with a total of 5 administrations. After a 7-day withdrawal, the animals were challenged with methamphetamine (0.5 mg/kg, i.p.). The effect of methamphetamine on locomotor activity was significantly potentiated by repeated adenosine pre-treatment. Moreover, methamphetamine-induced dopamine release was also increased in the striatum. Methamphetamine-induced hyperactivity and dopamine release were significantly potentiated by repeated pre-treatment of an adenosine A₁ agonist, N⁶-cyclohexyladenosine (0.5 mg/kg, i.p.). These results suggest that the acute effect of methamphetamine is potentiated by repeated pre-treatment of adenosine via adenosine A₁ receptors.