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 D(1)/D(2) receptor agonist apomorphine, as well as the modulatory effects of (S)-(-)-sulpiride (selective D(2) receptor antagonist) and domperidone (peripheral D(2) 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 D(2) 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.
Pelissier
Teresa
T
Programa de Biología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Chile. tpelissi@machi.med.uchile.cl
Laurido
Claudio
C
Hernandez
Alejandro
A
Constandil
Luis
L
Eschalier
Alain
A
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors
D000700:Analgesics; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D005557:Formaldehyde; D004294:Domperidone; D013469:Sulpiride; D001058:Apomorphine