Role of dopamine D(1) receptors for kappa-opioid-mediated locomotor activity and antinociception during the preweanling period: a study using D(1) receptor knockout mice.
kappa-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 kappa-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 kappa-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, kappa-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 kappa-opioid-mediated locomotor activity and antinociception during the preweanling period.
Karper
P E
PE
Department of Psychology, California State University, San Bernardino, CA 92407, USA.
Nazarian
A
A
Crawford
C A
CA
Drago
J
J
McDougall
S A
SA
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000701:Analgesics, Opioid; D017447:Receptors, Dopamine D1; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer