Dopaminergic involvement in adenosine A1 receptor-mediated antinociception in the tail flick latency model in mice

The interaction between the adenosinergic and dopaminergic systems in nociception was assessed in the tail flick latency (TFL) test in mice. Adenosine exhibited qualitatively different responses depending on the dose: Adenosine 10 and 100 mg/kg i.p. caused antinociception as evidenced by an increase in TFL while the middle dose of 30 mg/kg decreased TFL. On the other hand, the specific adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) at doses of 0.05, 0.1, 0.25 and 0.5 mg/kg (i.p.) resulted in dose-dependent antinociception. The antinociceptive effect of CPA was reversed by classical albeit nonspecific adenosine receptor antagonist theophylline (5 mg/kg) at a dose which had no effect on TFL per se. A low dose (1 mg/kg i.p.) of the dopaminergic agonist apomorphine caused an early mild hyperalgesic response while the high dose (10 mg/kg i.p.) had no significant effect on TFL. The antinociceptive effect of CPA was attenuated by pretreatment with low dose apomorphine while pretreatment with the high dose caused mild but insignificant potentiation. Theophylline, when administered prior to apomorphine failed to modify the nociceptive response. The results suggest that an interaction between adenosine and dopamine may be involved in nociception.