Neuropharmacology
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Dose-responsive motor activity induced by systemic injection of the kappa (kappa) preferring opioid agonist, U50,488H (1-10 mg/kg, s.c.) in guinea pigs was recently reported [Brent P. J. and Bot G. (1992) Psychopharmacology 107: 581-590], characterised at the higher doses used (5-10 mg/kg) by sustained postural abnormalities. The effects on the U50,488H-induced, abnormal, motor response of pharmacological manipulation of opioid receptors and sigma (sigma) sites was studied. ⋯ In addition, haloperidol (1 and 5 mg/kg, s.c.), dextromethorphan (10 mg/kg, s.c.) and DTG (30 mg/kg, s.c.), given in combination with U50,488H, induced behaviour characterised by marked oral activity. In contrast to the effect of haloperidol, pretreatment with the selective dopamine D-2 antagonist, raclopride (10 mg/kg, s.c.), had no significant effect on the abnormal movements induced by U50,488H, but did induce oral activity. These data indicate the possible involvement of kappa opioid receptors in the abnormal movement induced by U50,488H, and further demonstrate that there is an interaction between the kappa receptors and sigma sites which can influence the abnormal motor activity.