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.