Kappa opioid mediated locomotor activity in the preweanling rat: role of pre- and postsynaptic dopamine receptors

Abstract

 Treatment with a non-selective DA receptor agonist (i.e., NPA) has previously been shown to attenuate the kappa opioid mediated locomotor activity of preweanling rats. The purpose of the present study was to determine whether stimulation of D₁-like or D₂-like receptors is responsible for this behavioral effect and whether the critical DA receptors are located pre- or postsynaptically. To assess these questions, 17-day-old rats were injected with saline, the D₂/D₃ agonist quinpirole (0.1, 0.3, or 1.0 mg/kg, IP), or the D₁ agonist SKF 38393 (7.5, 15, or 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 activating effects of U-50,488 were blocked by the D₂/D₃, but not the D₁, receptor agonist. To dissociate the effects of DA autoreceptors and postsynaptic receptors, 17-day-old rats were given α-methyl-dl-p-tyrosine (AMPT reduces endogenous DA stores) prior to U-50,488 or amphetamine (1.5 mg/kg, SC) treatment. Interestingly, AMPT (which reduced DA levels by more than 80%) fully attenuated amphetamine-induced locomotor 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, these results indicate that kappa opioid stimulation enhances locomotor activity regardless of presynaptic DA levels. Similarly, quinpirole appears to attenuate U-50,488-induced locomotor activity by stimulating postsynaptic D₂-like receptors, since the D₂/D₃ agonist inhibited kappa opioid mediated behavior independent of endogenous DA levels.