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 role of central dopaminergic systems in mouse locomotor activity and analgesia by spiradoline mesylate. Analgesic activities of the kappa-opioid-receptor agonists spiradoline and U-50488H were not altered by haloperidol or L-dopa, whereas morphine analgesia was enhanced by haloperidol but attenuated by L-dopa. Spiradoline decreased spontaneous locomotor activity in mice and inhibited methamphetamine- or morphine-induced locomotor activity. In contrast, morphine given alone increased locomotor activity and enhanced methamphetamine-induced locomotor activity. In a neurochemical study, spiradoline decreased the amounts of dopamine metabolites in the striatum, but did not alter them in the brainstem and cerebral cortex. Morphine increased the dopamine metabolite contents in all three brain regions tested. These results suggest that inhibition of the dopaminergic pathway in the brain by spiradoline may be involved in its suppression of locomotor activity, but not in its analgesia; whereas, stimulation of the dopaminergic pathway by morphine seems to function in both behaviors: enhancement of locomotor activity and inhibition of analgesia.
Kunihara
M
M
Department of Pharmacology, Tsukuba Research Laboratories, Upjohn Pharmaceuticals, Ltd., Ibaraki, Japan.
Ohyama
M
M
Nakano
M
M
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*
D000700:Analgesics; D011759:Pyrrolidines; D008694:Methamphetamine; D007980:Levodopa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D006220:Haloperidol; C051272:spiradoline; D004298:Dopamine