Purine involvement in morphine antinociception

The effects of a series of adenosine derivatives on morphine antinoceptive effect were investigated in rats by the 'tail-flick' method. 2-Chloroadenosine (CADO) and L-N6-phenylisopropyladenosine (L-PIA), given intraperitoneally, caused decreased morphine antinociception. Intracerebroventricular injections of CADO, L-PIA and 5'-N-ethylcarboxamide adenosine (NECA), but not of 2'-deoxyadenosine, antagonized morphine antinociception. The effects of both central and peripheral injections of CADO and L-PIA on morphine antinociception were partially reversed by caffeine. Intracerebroventricular injection of dibutyryl-cyclic 3', 5' adenosine monophosphate (db cyclic AMP) had no effect on morphine antinociception. These data indicate that adenosine plays a role in morphine-induced antinociception. The results are discussed in terms of postulated effects of adenosine derivatives on adenylate cyclase.