Opposing effect of apomorphine on antinociceptive activity of morphine: a dose-dependent phenomenon.
Apomorphine, when administered intracerebroventricularly (0.05 mg/kg) to rats, increased tail-flick latency (a spinal nociceptive response). However, intraperitoneal administration at doses of 1, 3 and 10 mg/kg had no effect, probably because of a tonic supraspinal inhibitory influence on spinal dopaminergic neurones involved in segmental nociceptive processes. Depending on the doses administered, intraperitoneal administration of apomorphine exhibited opposite effects on antinociceptive activity of morphine. Pretreatment with a low dose of apomorphine (1 mg/kg) attenuated, whereas, a high dose (10 mg/kg) potentiated morphine-induced antinociception. Dopamine antagonists, in doses that preferentially block autoreceptors, i.e., haloperidol (0.1 mg/kg, i.p.) and (-)-sulpiride (5 mg/kg, i.p.), antagonised the attenuation of morphine antinociception by a low dose of apomorphine, while treatment with a high dose of haloperidol (1 mg/kg, i.p.) and pimozide (1.25 mg/kg, i.p.) completely antagonised the potentiating effect of a high dose of apomorphine on the antinociceptive activity of morphine. The attenuation of morphine antinociception thus appears to be due to decreased dopaminergic activity as a result of preferential dopamine autoreceptor stimulation by a low dose of apomorphine, whereas potentiation with a high dose of apomorphine is caused by enhanced dopaminergic activity via postsynaptic receptor stimulation.
Gupta
Y K
YK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029 India.
Chugh
Anita
A
Seth
S D
SD
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000502:physiology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D009020:Morphine; D001058:Apomorphine