Blockade of the morphine-induced increase in turnover of dopamine on the mesolimbic dopaminergic system by kappa-opioid receptor activation in mice.
Activation of central mu opioid receptors by treatment with systemic morphine elevates 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels without changing dopamine (DA) and 5-hydroxytryptamine (5-HT: serotonin) steady-state levels in the mouse limbic forebrain (including nucleus accumbens and olfactory tubercle). Pretreatment with systemic U-50,488H, a selective kappa agonist, could dose-dependently block the morphine-induced increase in turnover of DA. This blocking action by treatment with U-50, 488H was completely reversed by nor-binaltorphimine (nor-BNI), a selective kappa antagonist. On the other hand, U-50,488H did not affect the enhancement of 5-HT turnover induced by morphine. These findings suggest that kappa receptor activation can inhibit the mu agonist-induced activation of mesolimbic DA pathway but not ascending 5-HT pathway.
Department of Pharmacology, School of Pharmacy, Hosi University, Tokyo, Japan.
M
M
Narita
T
T
Suzuki
M
M
Funada
M
M
Misawa
H
H
Nagase
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*
D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D012701:Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D004298:Dopamine