Role of dopamine D 1 receptors for κ-opioid–mediated locomotor activity and antinociception during the preweanling period : a study using D 1 receptor knockout mice

Abstract

κ-Opioid receptor agonists both increase the locomotor activity of preweanling rats and induce antinociception. To determine whether dopamine (DA) D 1 receptors are necessary for either of these κ-opioid–mediated effects we used D 1 (D 1A) receptor knockout mice (i.e., D 1-deficient mice). Heterozygous, wild-type, and D 1-deficient mice (13 days old at testing) were injected with the κ-opioid receptor agonist U-50,488 methanesulfonate (0.0, 0.2, 1.0, 2.5, or 5.0 mg/kg, s.c.) and locomotor activity was measured for 60 min. In a separate experiment, tail-flick latencies of heterozygous, wild-type, and D 1-deficient 13-day-old mice were assessed both before and after treatment with U-50,488 (0.0, 1.0, 2.5, 5.0, or 10.0 mg/kg, s.c.). Results showed that lower doses of U-50,488 (0.2 and 1.0 mg/kg) increased the locomotor activity of 13-day-old mice regardless of genotype. Besides affecting locomotion, κ-opioid receptor stimulation induced antinociception in preweanling mice, as U-50,488 caused a dose-dependent increase in the tail-flick latencies of heterozygous, wild-type, and D 1-deficient mice. U-50,488's locomotor activating and analgesic effects did not differ according to genotype, thus suggesting that D 1 receptors are not necessary for κ-opioid–mediated locomotor activity and antinociception during the preweanling period.