We studied the effects of adenosine A1 and A(2A) receptor agonists on the expression and development of methamphetamine-induced sensitization in rats. When animals were treated with the adenosine A1 receptor agonist, N6- cyclohexyladenosine (CHA), along with methamphetamine every 3 days with a total of five administrations, the augmentation of hyperlocomotion by methamphetamine re-administration after 7-day withdrawal (methamphetamine challenge administration) was not inhibited. However, when the adenosine A(2A) receptor agonist, 2-p-(2-carboxyethyl) phenethyl-amino-5'-N- ethylcarboxy-amide adenosine (CGS21680), was administered according to the same schedule, the augmentation was significantly inhibited. On the other hand, when CHA or CGS21680 was administered 30 min before methamphetamine challenge, both drugs dose-dependently inhibited the augmentation of hyperlocomotion. These results suggested that both adenosine A1 and A(2A) receptors play important roles in the expression of methamphetamine-induced sensitization, and that adenosine A(2A) receptors do so in the development of this sensitization.
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