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Opposite effects of mu and kappa opiates on the firing-rate of dopamine cells in the substantia nigra of the rat.

Single unit extracellular recording was carried out in rats to compare the actions of a mu receptor agonist (morphine) to a kappa receptor agonist (U50,488) in the substantia nigra pars compacta (SNC). Intravenously administered morphine and U50,488 exhibited opposite effects: morphine excited SNC dopamine cells, and U50,488 inhibited them. Both effects were blocked by naloxone, although significantly more naloxone was necessary to block the effect of the kappa agonist. Local administration of U50,488 in the caudate also inhibited the firing of SNC dopamine cells. These results are discussed in terms of the natural functions of the prodynorphinergic straiatonigral projection.