EFFECTS OF SPIRADOLINE MESYLATE, A SELECTIVE KAPPA-OPIOID-RECEPTOR AGONIST, ON THE CENTRAL DOPAMINE SYSTEM WITH RELATION TO MOUSE LOCOMOTOR-ACTIVITY AND ANALGESIA

Neurochemical and behavioral investigations were made to assess the ro le of central dopaminergic systems in mouse locomotor activity and ana lgesia by spiradoline mesylate. Analgesic activities of the kappa-opio id-receptor agonists spiradoline and U-50488H were not altered by halo peridol or L-dopa, whereas morphine analgesia was enhanced by haloperi dol but attenuated by L-dopa. Spiradoline decreased spontaneous locomo tor activity in mice and inhibited methamphetamine- or morphine-induce d locomotor activity. In contrast, morphine given alone increased loco motor activity and enhanced methamphetamine-induced locomotor activity . In a neurochemical study, spiradoline decreased the amounts of dopam ine metabolites in the striatum, but did not alter them in the brainst em and cerebral cortex. Morphine increased the dopamine metabolite con tents in all three brain regions tested. These results suggest that in hibition of the dopaminergic pathway in the brain by spiradoline may b e involved in its suppression of locomotor activity, but not in its an algesia; whereas, stimulation of the dopaminergic pathway by morphine seems to function in both behaviors: enhancement of locomotor activity and inhibition of analgesia.