kappa-Opioid receptors in the substantia nigra pars reticulata mediate the U-50,488-induced locomotor activity of preweanling rats.

The purpose of the present study was to determine the neuroanatomical location where kappa-opioid receptor stimulation induces locomotor activity in the preweanling rat. To confirm that the U-50,488-induced locomotor activity of preweanling rats is mediated by kappa-opioid receptors, 18-day-old rats were initially injected with vehicle or the kappa-opioid receptor agonist U-50,488 (5 mg/kg, s.c.) followed, 15 min later, by an injection of the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, 8, or 12 mg/kg, s.c.). In subsequent experiments, 18-day-old rats were injected with vehicle or U-50,488 (5 mg/kg, s.c.) 15 min prior to bilateral administration (0.25 or 0.5 microl per side) of nor-BNI (0, 5, 10, or 20 microg) into the substantia nigra pars reticulata (SNR) or medial dorsal striatum (MDS). In the final experiment, 18-day-old rats received bilateral administration (0.25 microl per side) of vehicle or U-50,488 (0.0, 0.8, 1.6, or 3.2 microg) into the SNR. Results showed that systemically administered nor-BNI (0-12 mg/kg, s.c.) produced a dose-dependent reduction in the U-50, 488-induced locomotor activity of preweanling rats. The site of action for U-50,488's locomotor-activating effects appeared to be the SNR, because (a) bilateral administration of nor-BNI (5, 10, or 20 microg) into the SNR caused a complete attenuation of U-50, 488-induced locomotion, and (b) bilateral administration of U-50,488 into the SNR caused a dose-dependent increase in the locomotor activity of preweanling rats. Striatal injections of nor-BNI did not affect U-50,488-induced locomotor activity. When these findings are considered together it is apparent that stimulation of kappa-opioid receptors in the SNR is both necessary and sufficient for the occurrence of U-50,488-induced locomotor activity in the preweanling rat.