The effects of maternally administered sustained-release naltrexone on the developing rat brain

Waleed Farid

    Research output: ThesisDoctoral Thesis

    587 Downloads (Pure)


    [Truncated abstract] Oral methadone (opioid receptor agonist) is used to treat opioid dependence and is commonly accepted for management of pregnant addicts. Oral naltrexone (opioid receptor antagonist), is used to treat alcohol and opioid dependence but is associated with poor patient compliance and, due to lack of data on its safety in pregnant humans, is not recommended for use during pregnancy. Sustained-release preparations have been developed to overcome non-compliance. However, following the advent of a long-acting subcutaneous naltrexone-poly(DL-lactide) implant, there have been cases of inadvertent fetal and neonatal exposure. To date, human neonates exposed to naltrexone appear healthy with normal APGAR scores, head circumferences and birth-weight. Conversely, studies in pregnant rodents using higher naltrexone doses and different routes of administration to those used clinically, show drastic changes to various developmental parameters in offspring. In a pilot study (Cohort 1), clinically relevant rat models were developed to deliver naltrexone (custom-made sustained-release implants) or methadone (daily oral methadone) to pregnant mothers. Following naltrexone exposure, litter sizes were larger and, although offspring birth-weight was reduced, brain morphometry was unaltered; there was an overall lack of effect from methadone. The primary objective of the present study was to extend these findings and examine the safety of maternally administered oral methadone or sustained-release naltrexone primarily on offspring.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2010


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