@article{191f826dcb7d46f89efafa7851eb326d,
title = "Early life stress alters the developmental trajectory of corticolimbic endocannabinoid signaling in male rats",
abstract = "Early-life stress modulates the development of cortico-limbic circuits and increases vulnerability to adult psychopathology. Given the important stress-buffering role of endocannabinoid (eCB) signaling, we performed a comprehensive investigation of the developmental trajectory of the eCB system and the impact of exposure to early life stress induced by repeated maternal separation (MS; 3 h/day) from postnatal day 2 (PND2) to PND12. Tissue levels of the eCB molecules anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured after MS exposures, as well under basal conditions at juvenile (PND14), adolescent (PND40) and adult (PND70) timepoints in the prefrontal cortex (PFC), amygdala and hippocampus. We also examined the effects of MS on CB1 receptor binding in these three brain regions at PND40 and PND70. AEA content was found to increase from PND2 into adulthood in a linear manner across all brain regions, while 2-AG was found to exhibit a transient spike during the juvenile period (PND12-14) within the amygdala and PFC, but increased in a linear manner across development in the hippocampus. Exposure to MS resulted in bidirectional changes in AEA and 2-AG tissue levels within the amygdala and hippocampus and produced a sustained reduction in eCB function in the hippocampus at adulthood. CB1 receptor densities across all brain regions were generally found to be downregulated later in life following exposure to MS. Collectively, these data demonstrate that early life stress can alter the normative ontogeny of the eCB system, resulting in a sustained deficit in eCB function, particularly within the hippocampus, in adulthood.",
author = "Hill, {Matthew N.} and Lisa Eiland and Lee, {Tiffany T.Y.} and Hillard, {Cecilia J.} and McEwen, {Bruce S.}",
note = "Funding Information: The authors would like to thank Praveen Chatani for his technical assistance. This research was supported operating funds from the National Institutes of Health to BSM ( R01 MH041256 ) and CJH ( R01 DA026996 ), with additional support to CJH from the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin . MNH was the recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research and TTL was the recipient of a doctoral fellowship from CIHR . Funding for this study was also provided to LE by a Weill Cornell Medical College Friedman Clinical Scholarship in Newborn Medicine and by a National Institute of Mental Health Diversity Supplement 3R01MH041256-22S1 . MNH currently receives salary support in the form of a Tier II Canada Research Chair supported by the CIHR . All funding bodies had no role in the design, acquisition or interpretation of this data or in the writing of, or decision to submit, this manuscript. Funding Information: The authors would like to thank Praveen Chatani for his technical assistance. This research was supported operating funds from the National Institutes of Health to BSM (R01 MH041256) and CJH (R01 DA026996), with additional support to CJH from the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin. MNH was the recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research and TTL was the recipient of a doctoral fellowship from CIHR. Funding for this study was also provided to LE by a Weill Cornell Medical College Friedman Clinical Scholarship in Newborn Medicine and by a National Institute of Mental Health Diversity Supplement 3R01MH041256-22S1. MNH currently receives salary support in the form of a Tier II Canada Research Chair supported by the CIHR. All funding bodies had no role in the design, acquisition or interpretation of this data or in the writing of, or decision to submit, this manuscript. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = mar,
day = "1",
doi = "10.1016/j.neuropharm.2018.11.036",
language = "English",
volume = "146",
pages = "154--162",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Ltd.",
}