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Title: Ontogenesis of central opioid systems in rats perinatally exposed to lead
Author: McDowell, Julia
ISNI:       0000 0001 3623 8932
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1988
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The literature relating to the ontogeny of the opioid system and to the toxic effects of lead in both man and animals with particular reference to neurochemical and behavioural toxicity of lead is reviewed. The effects of perinatal lead exposure on the development of several aspects of opioid function has been studied using a dosing model of lead (as the acetate) in the maternal drinking water from conception until postnatal day 14 or 21. This model of low level perinatal lead exposure in rats had no toxic effects on growth and produced blood lead levels close to the safety limits set for human exposure and similar to those that have been recorded in some children. The ontogeny of morphine antinociception using the tail immersion test and ketocyclazocine in the paw pressure test was studied in 10,21 and 30 day old rats. Perinatal lead exposure decreased the antinociceptive activity of both morphine and ketocyclazocine in 10 day old rats. Recovery of morphine antinociception occured by 21 days and ketocyclazocine antinociception by 30 days. Radioligand binding studies with [3H]DAGO were used to study the ontogeny of u-opioid receptors in 10,21 and 30 day old rats. Perinatal lead exposure was without effect on equilibrium dissociation constant or maximal binding capacity. Radioligand binding studies with [[3]H] DPDPE were used to study the ontogeny of 6 -opioid receptors in rats between 15 and 50 days. The affinity of the 6-opioid binding site for [[3]H] DPDPE was reduced by perinatal lead exposure but without accompanying changes in binding capacity. This effect of lead on s-opioid receptors was persistant and was observed in rats aged 15-50 days. Basal plasma corticosterone levels (measured fluorimetrically) were elevated by perinatal lead exposure in 45 and 60 day old rats but not in 30 day old rats. In addition the modulatory effect of morphine on stress induced elevations of corticosterone levels was also affected by lead exposure. A reduced effect of morphine was seen in 30 day old animals whilst an increased effect was seen in 60 day old animals. Locomotor activity (measured by photocell detection) of 10,21 and 30 day old rats was recorded over 1 hour during the dark phase of the light/dark cycle. Exploratory locomotor activity was reduced in lead exposed animals at postnatal day 10 and the hypolocomotor effect of morphine was also increased in 10 day old lead exposed animals. The opioid system is particularly sensitive to perinatal low level lead exposure and this is manifested in several aspects of physiological function. Possible mechanisms by which lead affects the development of the opioid system are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Toxic effects of lead][Rat opioid system