Inhibition of anandamide hydrolysis dampens the neuroendocrine response to stress in neonatal rats subjected to suboptimal rearing conditions.

TitleInhibition of anandamide hydrolysis dampens the neuroendocrine response to stress in neonatal rats subjected to suboptimal rearing conditions.
Publication TypeJournal Article
Year of Publication2016
AuthorsMcLaughlin RJoseph, Verlezza S, Gray JMegan, Hill MNicholas, C-D Walker
JournalStress
Volume19
Issue1
Pagination114-24
Date Published2016
ISSN1607-8888
KeywordsAdrenocorticotropic Hormone, Amidohydrolases, Animals, Animals, Newborn, Arachidonic Acids, Behavior, Animal, Benzamides, Carbamates, Corticosterone, Endocannabinoids, Hydrolysis, Hypothalamus, Male, Neurosecretory Systems, Paraventricular Hypothalamic Nucleus, Polyunsaturated Alkamides, Rats, Rats, Sprague-Dawley, Restraint, Physical, Stress, Physiological, Stress, Psychological
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.

DOI10.3109/10253890.2015.1117448
Alternate JournalStress
PubMed ID26552023
Grant List / / Canadian Institutes of Health Research / Canada