Maternal separation and early stress cause long‐lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats

Abstract

A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 × 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016.

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

“…However, in adulthood, PS was found to reduce spine density and dendritic branching and length in dACC and orbitofrontal cortex layer II/III pyramidal neurons (Murmu et al, 2006), and to reduce the ratio of mushroom spines; the type forming the most strong and stable synapses (Michelsen et al, 2007). ESD was also found to reduce apical dendritic length in several PFC subregions in the adult offspring, and reduce spine density in frontal cortex layer III neurons (Monroy et al, 2010; Romano-López et al, 2016). Reduced local expression of BDNF mRNA in adult MS (Roceri et al, 2004), LN (Roth et al, 2009), and PS offspring due to increased Bdnf DNA methylation [associated with an increase in DNA methyltransferase 1 (DNMT1) expression; Roth et al, 2009; Dong et al, 2015], may relate to these changes.…”

Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms

“…For example, MD results in sexually dimorphic decreases of cannabinoid receptor type 1 (CB 1 ) receptor expression and increases in CB 2 receptor expression and altered levels of enzymes involved in the biosynthesis and degradation of endocannabinoids in the hippocampus of P13 rodents (Suarez et al, ). In adolescence, several genes encoding components of the endocannabinoid system were increased in the frontal cortex of males and the hippocampus of females exposed to MD (Marco et al, ), and changes in the endocannabinoid system have been reported in the nucleus accumbens and frontal cortex of MS rats (Romano‐Lopez et al, ). Furthermore, early‐life stress is well known to induce depressive‐ and anxiety‐like behavioral phenotypes in adulthood (Daniels et al, ; Llorente et al, ; Marco et al, ), and recent studies from our laboratory have demonstrated an important role for anandamide activation of CB 1 receptors in the rostral ventromedial medulla in a rat model of hyperalgesia associated with depression/anxiety (Rea et al, ).…”

Effects of early life stress on biochemical indicators of the dopaminergic system: a 3 level meta-analysis of rodent studies

“…Ling et al 2004; Z. Ling et al 2009; Liu et al 2016; Lovic et al 2013; Luchicchi et al 2016; Madruga et al 2006; Matthews et al 2001; Meyer, Nyffeler, Schwendener, et al 2008; Meyer, Nyffeler, Yee, et al 2008; Novak et al 2013; Ognibene et al 2008; Oreland et al 2011; Ozawa et al 2006; Pallarés et al 2013; Panagiotaropoulos et al 2004; Pang et al 2015; Papaioannou et al 2002; Ploj, Roman, and Nylander 2003; Rentesi et al 2013; Reynaert et al 2016; Reznikov and Nosenko 1995; Romano-López et al 2015; Eva Romero et al 2007; E Romero et al 2010; Rossi-George et al 2011; Rots et al 1996; Sasagawa et al 2017; Silvagni et al 2008; Silveira et al 2010; Son et al 2007; Tien et al 2013; Vazquez et al 2007; Vuillermot et al 2012; Wang et al 2009; Weston, Sobolewski, et al 2014; Weston, Weston, et al 2014; Winter et al 2009; Womersley et al 2011; Zager, Mennecier, and Palermo-Neto 2012; Zavitsanou et al 2013; Y. Zhang et al 2015; X.…”