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

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The purpose of the present study was to determine the neuroanatomical location where κ-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 κ-opioid receptors, 18-day-old rats were initially injected with vehicle or the κ-opioid receptor agonist U-50,488 (5 mg/kg, s.c.) followed, 15 min later, by an injection of the κ-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 μl per side) of nor-BNI (0, 5, 10, or 20 μg) 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 μl per side) of vehicle or U-50,488 (0.0, 0.8, 1.6, or 3.2 μg) 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 μg) 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 κ-opioid receptors in the SNR is both necessary and sufficient for the occurrence of U-50,488-induced locomotor activity in the preweanling rat.