Altered neurochemical and behavioral development of 10-day-old rats perinatally exposed to the kappa opioid agonist U-50,488H.

To determine the effects of chronic perinatal exposure to a kappa opioid agonist on the neurochemical and motor development of rat offspring, osmotic pumps containing trans-(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U-50,488H), 79 mg/ml, or vehicle were implanted into anesthetized pregnant female rats. On postnatal day 10, the nucleus accumbens (NAc) of male offspring were dissected and assayed for dopamine (DA) receptors. Male offspring from other litters were injected subcutaneously with the D2 agonist quinpirole, 0.05 mg/kg, the D1 agonist SKF 38393, 10 mg/kg, or 0.9% saline vehicle. Their locomotor activity was then monitored for 1 h. The binding of DA D1 and D2 receptors was significantly increased by 26% and 90%, respectively, in the NAc of 10-day-old offspring exposed to U-50,488H. There was a significant, 52%, decrease in the locomotor response to quinpirole by 10-day-old offspring exposed to U-50,488H. Exposure to U-50,488H had no significant effect on the locomotor response to SKF 38393 at this age. The results indicate that perinatal exposure to a kappa agonist alters the development of brain DA receptors and DA-mediated motor behavior. The data suggest that motor deficits observed in offspring exposed to opioids in utero may involve brain kappa opioid receptor mechanisms.