Inhibitory effects of the kappa opiate U50,488 in the substantia nigra pars reticulata.

The effect of the selective kappa opiate agonist U50,488 on the firing rate of neurons of the substantia nigra pars reticulata (SNR) was investigated in a series of extracellular single unit recording experiments in rats. Intravenous administration of U50,488 produced a dose-related decrease in the spontaneous firing rate of SNR neurons, an effect that was reversed by naloxone in most cases. Iontophoretic application of the kappa agonist also inhibited the firing of SNR neurons, indicating a direct action of U50,488 in the SNR. U50,488 was particularly effective in inhibiting a local group of SNR neurons that exhibit increased firing in response to mechanical pressure. In separate experiments, it was determined that these pressure sensitive neurons (1) include nigrotectal and nigrothalamic cells, (2) are responsive to mild as well as painful levels of pressure, and (3) are not responsive to light flashes. This group of neurons may be a primary target of naturally occurring kappa selective opioids of the prodynorphinergic striatonigral pathway.