Long-term consequences of perinatal fatty acid amino hydrolase inhibition

Autor:	Corinne M. Spencer, Ken Mackie, Traci A. Czyzyk, Chris P. Haskins, Heather B. Bradshaw, Chia Shan Wu, Hui-Chen Lu, Emma Leishman, Mary Jeanette Andrews, Chris P. Jew, Daniel J. Morgan
Rok vydání:	2014
Předmět:	Pharmacology chemistry.chemical_classification medicine.medical_specialty Perinatal Exposure medicine.medical_treatment Fatty acid Anandamide URB597 Biology Endocannabinoid system chemistry.chemical_compound Endocrinology chemistry Fatty acid amide hydrolase Internal medicine Toxicity medicine Cannabinoid
Zdroj:	British Journal of Pharmacology. 171:1420-1434
ISSN:	0007-1188
Popis:	Background and Purpose Fatty acid amide hydrolase inhibitors show promise as a treatment for anxiety, depression and pain. Here we investigated whether perinatal exposure to URB597, a fatty acid amide hydrolase inhibitor, alters brain development and affects behaviour in adult mice. Experimental Approach Mouse dams were treated daily from gestational day 10.5 to 16.5 with 1, 3 or 10 mg kg−1 URB597. MS was used to measure a panel of endocannabinoids and related lipid compounds and brain development was assessed at embryonic day 16.5. Separate cohorts of mouse dams were treated with 10 mg kg−1 URB597, from gestational day 10.5 to postnatal day 7, and the adult offspring were assessed with a battery of behavioural tests. Key Results Perinatal URB597 exposure elevated anandamide and related N-acyl amides. URB597 did not induce signs of toxicity or affect dam weight gain, neurogenesis or axonal development at embryonic day 16.5. It did lead to subtle behavioural deficits in adult offspring, manifested by reduced cocaine-conditioned preference, increased depressive behaviours and impaired working memory. Anxiety levels, motor function and sensory-motor gating were not significantly altered. Conclusions and Implications Taken together, the present results highlight how exposure to elevated levels of anandamide and related N-acyl amides during brain development can lead to subtle alterations in behaviour in adulthood. Linked Articles This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::c695d3364a6e59fc07c3f6b6c3733b97 https://doi.org/10.1111/bph.12500 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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