Effect of perinatal lead treatment on morphine dependence in the adult rat

The effect of perinatal lead exposure (at 300 and 1000 ppm in the maternal drinking water from conception to postnatal day 14) on the opioid withdrawal syndrome in adult offspring has been studied to assess if lead produces long term disruption of opioid systems manifested as altered morphine dependence. Dependence was induced in 50 day old rats by administration of morphine in osmotic mini-pumps implanted subcutaneously and delivering 5, 15 or 40 mg/kg/day. At postnatal day 55 an opioid withdrawal syndrome was precipitated by administration of naloxone (4 mg/kg i.p) and withdrawal behaviour scored over the next 30 min. Both objective (jumping, weight loss, weight of excreta, wet dog shakes, mouthing and face washing) and subjective (teeth chatter, ptosis, diarrhoea, irritability) measures were scored. 60 min after naloxone animals were killed and plasma corticosterone measured as a biochemical index of withdrawal. Morphine withdrawal scores and plasma corticosterone exhibited a clear dose relationship and there were no significant differences between 0 and 300 ppm lead-exposed groups. However withdrawal scores in 1000 ppm lead-exposed animals were lower in 15 and 40 mg/kg morphine treated rats, predominantly associated with lower weight loss, wet dog shakes and mouthing responses. Paradoxically corticosterone levels were elevated in the 40 mg/kg morphine dose group. The results support other evidence that perinatal lead exposure can induce disruption in opioid functioning which persists to adulthood and suggest a possible link between lead and opioid addiction.