Paradoxical effects of kappa-opioid stimulation on the locomotor activity and Fos immunoreactivity of the preweanling rat: role of dopamine receptors

The kappa-opioid agonist U-50,488 increases the locomotor activity of preweanling rats. The authors attempted to determine whether this effect was modulated by dopamine (DA) system functioning. Surprisingly, U-50,488's locomotor activating effects were attenuated by both the DA receptor antagonist flupenthixol and the DA receptor agonist R(-)-propylnorapomorphine (NPA). In order to determine those brain areas stimulated by U-50,488, Fos immunoreactivity was assessed in 17- and 80-day-old rats. U-50,488 not only enhanced the locomotor activity of the younger rats, but it also enhanced Fos expression in various brain areas, including the nucleus accumbens and medial striatum. NPA blocked U-50,488-induced Fos expression in the latter region. When considered together, these results indicate that U-50,488 does not increase locomotion by stimulating a DA mechanism. Instead, either agonizing or antagonizing DA receptors is sufficient to disrupt U-50,488's locomotor activating effects in the preweanling rat.