Institutional members access full text with Ovid®

Share this article on:

Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain

Marco, Eva M.a; Echeverry-Alzate, Victorb; López-Moreno, Jose Antoniob; Giné, Elenac; Peñasco, Saraa; Viveros, Maria Paza

doi: 10.1097/FBP.0000000000000068
Research Reports

The endocannabinoid system is involved in several physiological and pathological states including anxiety, depression, addiction and other neuropsychiatric disorders. Evidence from human and rodent studies suggests that exposure to early life stress may increase the risk of psychopathology later in life. Indeed, maternal deprivation (MD) (24 h at postnatal day 9) in rats induces behavioural alterations associated with depressive-like and psychotic-like symptoms, as well as important changes in the endocannabinoid system. As most neuropsychiatric disorders first appear at adolescence, and show remarkable sexual dimorphisms in their prevalence and severity, in the present study, we analysed the gene expression of the main components of the brain cannabinoid system in adolescent (postnatal day 46) Wistar male and female rats reared under standard conditions or exposed to MD. For this, we analysed, by real-time quantitative PCR, the expression of genes encoding for CB1 and CB2 receptors, TRPV1 and GPR55 (Cnr1, Cnr2a, Cnr2b, Trpv1, and Gpr55), for the major enzymes of synthesis, N-acyl phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) (Nape-pld, Dagla and Daglb), and degradation, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Faah, Magl and Cox-2), in specific brain regions, that is, the frontal cortex, ventral and dorsal striatum, dorsal hippocampus and amygdala. In males, MD increased the genetic expression of all the genes studied within the frontal cortex, whereas in females such an increase was observed only in the hippocampus. In conclusion, the endocannabinoid system is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain.

aDepartment of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, Institute of Biomedical Research of the San Carlos Clinical Hospital

bDepartment of Psychobiology, Faculty of Psychology, Campus de Somosaguas

cDepartment of Biochemistry, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain

Correspondence to Eva M. Marco, PhD, Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, C/ Jose Antonio Novais, no 12. 28040-Madrid, Spain E-mail:

Received February 28, 2014

Accepted June 22, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins