Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats

The effects of adult and perinatal lead treatment on the development of loc omotor sensitization produced with repeated morphine administration was inv estigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg /kg morphine sulfate or water vehicle (ip) and locomotor activity was monit ored for 14 consecutive days. While both control and lead-exposed animals d emonstrated a locomotor sensitization to morphine, the magnitude of the inc reased locomotor response was reduced in lead-treated animals. Subsequent a nalysis of blood-lead in the adult lead-exposed animals indicated residue l evels ranging between 20 and 30 mug/dl. In Experiment 2, adult female rats were treated daily with 0, 8, or 16 mg lead via gavage for 30 days before b reeding with non-exposed males. Lead exposure in dams continued through ges tation and until pups were weaned at postnatal day (PND) 21. At PND 60, mal e offspring received morphine or vehicle challenges identical to those desc ribed in Experiment 1. Animals perinatally exposed to dams receiving 16 mg lead daily demonstrated an enhanced behavioral response to morphine relativ e to control animals. Analysis of offspring blood indicated lead levels bel ow detectable limits (<1 <mu>g/dl) for all animals. The results suggest exp osure to lead at environmentally relevant levels produces long-lasting chan ges in drug-induced behavior, and the developmental period in which lead ex posure occurs is a significant contributor to the manifestation of these ef fects. (C) 2000 Elsevier Science Inc. All rights reserved.