Faculty Collaboration Database

Early life stress alters the developmental trajectory of corticolimbic endocannabinoid signaling in male rats. Neuropharmacology 2019 Mar 01;146:154-162

Date

11/30/2018

Pubmed ID

30496752

Pubmed Central ID

PMC6347425

DOI

10.1016/j.neuropharm.2018.11.036

Scopus ID

2-s2.0-85057629348 (requires institutional sign-in at Scopus site)   36 Citations

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 List

Hill MN, Eiland L, Lee TTY, Hillard CJ, McEwen BS

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amygdala
Animals
Arachidonic Acids
Endocannabinoids
Female
Glycerides
Hippocampus
Humans
Male
Maternal Deprivation
Polyunsaturated Alkamides
Prefrontal Cortex
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Stress, Psychological