EFFECTS OF SPIRADOLINE MESYLATE, A SELECTIVE KAPPA-OPIOID-RECEPTOR AGONIST, ON THE CENTRAL DOPAMINE SYSTEM WITH RELATION TO MOUSE LOCOMOTOR-ACTIVITY AND ANALGESIA
M. Kunihara et al., EFFECTS OF SPIRADOLINE MESYLATE, A SELECTIVE KAPPA-OPIOID-RECEPTOR AGONIST, ON THE CENTRAL DOPAMINE SYSTEM WITH RELATION TO MOUSE LOCOMOTOR-ACTIVITY AND ANALGESIA, Japanese Journal of Pharmacology, 62(3), 1993, pp. 223-230
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.