Effects of Adenosine A₁- and A_2A-Receptor Agonists on Enhancement of Dopamine Release From the Striatum in Methamphetamine-Sensitized Rats

Abstract

We report here both adenosine A₁- and A_2A-receptor agonists inhibit the expression of methamphetamine (MAP)-induced behavioral sensitization in rats. Animals were treated with MAP (1.0 mg /kg, i.p.) every 3 days with a total of 5 administrations. The augmentation of dopamine release from the striatum was demonstrated by MAP re-administration (0.5 mg/kg, i.p.) after 7-day withdrawal by microdialysis. The augmentation of dopamine release was inhibited by pre-treatment not with N6-cyclohexyladenosine (0.01 mg/kg, i.p.) but by with 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxy-amide adenosine (0.1 mg/kg, i.p.). These results suggested that adenosine A₁ and A_2A receptors play an inhibitory role in sensitization via different mechanisms.