KAPPA-OPIOID MEDIATED LOCOMOTOR-ACTIVITY IN THE PREWEANING RAT - ROLEOF PRESYNAPTIC AND POSTSYNAPTIC DOPAMINE-RECEPTORS

Treatment with a non-selective DA receptor agonist (i.e., NPA) has pre viously been shown to attenuate the kappa opioid mediated locomotor ac tivity of preweanling rats. The purpose of the present study was to de termine whether stimulation of D-1-like or D-2-like receptors is respo nsible for this behavioral effect and whether the critical DA receptor s are located pre-or postsynaptically. To assess these questions, 17-d ay-old rats were injected with saline, the D-2/D-3 agonist quinpirole (0.1, 0.3, or 1.0 mg/kg, IF), or the D-1 agonist SKF 38393 (7.5, 15, o r 30 mg/kg, IP), 20 min after receiving the kappa opioid agonist U-50, 488 (5 mg/kg, SC) or saline. Results showed that the locomotor activat ing effects of U-50,488 were blocked by the D-2/D-3, but not the D-1, receptor agonist. To dissociate the effects of DA autoreceptors and po stsynaptic receptors, 17-day-old rats were given alpha-methyl-DL-p-tyr osine (AMPT reduces endogenous DA stores) prior to U-50,488 or ampheta mine (1.5 mg/kg, SC) treatment. Interestingly, AMPT (which reduced DA levels by more than 80%) fully attenuated amphetamine-induced locomoto r activity, while having little effect on U-50,488-induced locomotion. In addition, quinpirole blocked the locomotor activating effects of U -50,488 in rats acutely depleted of DA. When considered together, thes e results indicate that kappa opioid stimulation enhances locomotor ac tivity regardless of presynaptic DA levels. Similarly, quinpirole appe ars to attenuate U-50,488-induced locomotor activity by stimulating po stsynaptic D-2-like receptors, since the D-2/D-3 agonist inhibited kap pa opioid mediated behavior independent of endogenous DA levels.