Influences of electrical lesions of the dopaminergic system on morphine- and U-50,488H-induced analgesia in rats.
The effects of electrical lesions of brain areas containing dopamine cell bodies and terminals on morphine analgesia were investigated and compared with those of a selective kappa-opioid agonist, U-50,488H. The analgesic effect of morphine 10 mg/kg IP was potentiated significantly in substantia nigra (SN)- or caudate-putamen-lesioned rats, but not by ventral tegmental area (VTA) or nucleus accumbens lesions. However, electrical lesions of neither SN nor VTA affected the analgesic activity of U-50,488H 32 mg/kg IP. Although the tolerance to morphine analgesia developed in all four of the lesioned groups as well as in sham-lesioned rats, a significant analgesic effect in the SN-lesioned group prevailed during chronic treatment for 14 days as compared with that of sham-lesioned rats. From these results, it is suggested that morphine analgesia is potentiated by dysfunction of the nigro-striatal dopaminergic system, but not by that of the mesolimbic dopaminergic system, the central dopaminergic system is not involved in the appearance of U-50,488H analgesia and is not basically related to the development of tolerance to morphine analgesia.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
T
T
Ueki
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D004298:Dopamine