Biphasic effect of apomorphine on rat nociception and effect of dopamine D2 receptor antagonists

Studies on the effect of dopaminergic agonists in behavioral measures of nociception have gathered numerous but rather conflicting data. We studied the effects of the D1/D2 receptor agonist apomorphine, as well as the modulatory effects of (S)-(−)-sulpiride (selective D2 receptor antagonist) and domperidone (peripheral D2 receptor antagonist), on thermal, mechanical and chemical nociception on rats. Apomorphine induced a biphasic dose–response relationship, low doses producing hyperalgesia and high doses inducing antinociception. Tonic (chemical) pain was more sensitive to apomorphine than phasic (thermal and mechanical thresholds) pain. (S)-(−)-sulpiride, but not domperidone, fully antagonized the antinociceptive effect of apomorphine in all three measures of nociception, pointing to a participation of D2 dopaminergic receptors for the antinociceptive action of apomorphine. Although spinal sites for dopaminergic ligands mechanistically may account for the effects observed, involvement of dopaminergic receptors of the forebrain could probably explain better the antinociceptive effects of apomorphine, especially in chemical tonic pain.