Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in Adulthood
MetadataShow full item record
Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the effects of maternally administered sustained-release naltrexone on the rat brain by examining offspring at birth and in adulthood. Maternal treatment (naltrexone or placebo implant) started before conception and ceased during gestation, birth or weaning. Morphometry was assessed in offspring at birth and adulthood. Adult offspring were evaluated for differences in locomotor behaviour (basal and morphine-induced, 10 mg/kg, s.c.) and opioid neurochemistry, propensity to self-administer morphine and cue-induced drug-seeking after abstinence. Blood analysis confirmed offspring exposure to naltrexone during gestation, birth and weaning. Naltrexone exposure increased litter size and reduced offspring birth-weight but did not alter brain morphometry. Compared to placebo, basal motor activity of naltrexone-exposed adult offspring was lower, yet they showed enhanced development of psychomotor sensitization to morphine. Developmental naltrexone exposure was associated with resistance to morphine-induced down-regulation of striatal preproenkephalin mRNA expression in adulthood. Adult offspring also exhibited greater operant responding for morphine and, in addition, cue-induced drug-seeking was enhanced. Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero.
This article is published under the Open Access publishing model and distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ Please refer to the licence to obtain terms for any further reuse or distribution of this work.
Showing items related by title, author, creator and subject.
Maternally Administered Sustained-Release Naltrexone in Rats Affects Offspring Neurochemistry and Behaviour in AdulthoodFarid, W.; Lawrence, A.; Krstew, E.; Tait, Robert; Hulse, G.; Dunlop, S. (2012)Naltrexone is not recommended during pregnancy. However, sustained-release naltrexone implant use in humans has resulted in cases of inadvertent foetal exposure. Here, we used clinically relevant dosing to examine the ...
Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent mannerWang, K.; Larcombe, Alexander; Berry, L.; Morton, J.; Davidge, S.; James, A.; Noble, P. (2018)Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlyingmechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on ...
Increased heterogeneity of airway calibre in adult rats after hypoxia-induced intrauterine growth restrictionWang, K.; Morton, J.; Davidge, S.; Larcombe, Alexander; James, A.; Donovan, G.; Noble, P. (2017)Background and objective: Intrauterine growth restriction (IUGR) is associated with asthma development. We hypothesized that IUGR disrupts airway development leading to postnatal structural abnormalities of the airway ...