title: Inhibition of anandamide hydrolysis dampens the neuroendocrine response to stress in neonatal rats subjected to suboptimal rearing conditions.
abstract: Exposure to stress during early development can exert profound effects on the maturation of the neuroendocrine stress axis. The endocannabinoid (ECB) system has recently surfaced as a fundamental component of the neuroendocrine stress response; however, the effect of early-life stress on neonatal ECB signaling and the capacity to which ECB enhancement may modulate neonatal stress responses is relatively unknown. The present study assessed whether exposure to early-life stress in the form of limited access to nesting/bedding material (LB) from postnatal (PND) day 2 to 9 alters neuroendocrine activity and hypothalamic ECB content in neonatal rats challenged with a novel immobilization stressor. Furthermore, we examined whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of anandamide (AEA) affects neuroendocrine responses in PND10 pups as a function of rearing conditions. Neonatal rats showed a robust increase in corticosterone (CORT) and adrenocorticotropin hormone (ACTH) secretion in response to immobilization stress, which was significantly blunted in pups reared in LB conditions. Accordingly, LB pups exhibited reduced stress-induced Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, with no significant differences in hypothalamic ECB content. Administration of the FAAH inhibitor URB597 (0.3 mg/kg, ip) 90 min prior to immobilization stress significantly dampened stress-induced CORT release, but only in pups reared in LB conditions. These results suggest that rearing in restricted bedding conditions dampens the neuroendocrine response to stress, while augmenting AEA mitigates stress-induced alterations in glucocorticoid secretion preferentially in pups subjected to early-life stress.
authors.affiliation: a Douglas Mental Health University Institute, McGill University , Montreal , QC , Canada .|b Department of Integrative Physiology & Neuroscience , College of Veterinary Medicine, Washington State University , Pullman , WA , USA , and.
authors.forename: Ryan Joseph
authors.initials: RJ
authors.lastname: McLaughlin
authors.affiliation: a Douglas Mental Health University Institute, McGill University , Montreal , QC , Canada .
authors.forename: Silvanna
authors.initials: S
authors.lastname: Verlezza
authors.affiliation: c Department of Cell Biology & Anatomy and Psychiatry , Hotchkiss Brain Institute, University of Calgary , Calgary , AB , Canada.
authors.forename: Jennifer Megan
authors.initials: JM
authors.lastname: Gray
authors.affiliation: c Department of Cell Biology & Anatomy and Psychiatry , Hotchkiss Brain Institute, University of Calgary , Calgary , AB , Canada.
authors.forename: Matthew Nicholas
authors.initials: MN
authors.lastname: Hill
authors.affiliation: a Douglas Mental Health University Institute, McGill University , Montreal , QC , Canada .
authors.forename: Claire-Dominique
authors.initials: CD
authors.lastname: Walker
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D006868:Hydrolysis; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000324:Adrenocorticotropic Hormone; D000581:Amidohydrolases; D001095:Arachidonic Acids; D001549:Benzamides; D002219:Carbamates; D003345:Corticosterone; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C078814:anandamide
keywords: Endocannabinoid; early-life stress; hypothalamus; limited bedding; maternal care; rat