Early life stress and susceptibility to addiction in adolescence

Age- and sex-specific effects of maternal separation on the acoustic startle reflex in rats: early baseline enhancement in females and blunted response to ambiguous threat

“…In rats, the sex-specific effect of MS on the startle response in adolescents has not been extensively studied. Previous studies have found adolescent females to be more susceptible to anxiety-like behavior after MS than male rats using other assays measuring defensiveness and hypervigilance (Jin et al, 2018 ; Tschetter et al, 2021 ). Similar effects have been seen in depressive-like behavior, specifically an earlier onset of depressive-like behavior after early life adversity in female adolescents compared to males (Goodwill et al, 2019 ).…”

“…MS has been shown to exert changes in CRF mRNA expression throughout the brain, including the central amygdala (CeA), BNST, medial PFC, locus coeruleus, and paraventricular nucleus of the hypothalamus (Plotsky and Meaney, 1993 ; Plotsky et al, 2005 ), all regions involved in the defensive response (LeDoux and Pine, 2016 ). Although adolescent-specific alterations are less extensively studied, one study found increased CRF mRNA in the PVN of adolescent female rats after MS, but no changes in the BNST or CeA, and no changes in males (Tschetter et al, 2021 ). Female adolescents exposed to MS demonstrate earlier manifestation of excitatory/inhibitory imbalances in the PFC, driven by reduced expression of GABAergic markers and hyperinnervation from the amygdala (Honeycutt et al, 2020 ; Ohta et al, 2020 ).…”

Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress

“…On test day, one of the familiar objects is replaced with a novel object and the time spent around the novel object area is expressed as a percentage to determine novelty-seeking responses [ 88 , 230 ]. A baseline sex difference has been observed in control males compared to control females during adolescence, which is characterized by a higher percentage of time spent interacting with the novel object [ 105 ]. However, only adolescent female MS rats exhibited enhanced novelty-seeking responses, as indexed by higher percentages of novel object exploration/interaction time and greater number of approach responses to the novel object, compared to control adolescent females [ 105 ].…”

“…A baseline sex difference has been observed in control males compared to control females during adolescence, which is characterized by a higher percentage of time spent interacting with the novel object [ 105 ]. However, only adolescent female MS rats exhibited enhanced novelty-seeking responses, as indexed by higher percentages of novel object exploration/interaction time and greater number of approach responses to the novel object, compared to control adolescent females [ 105 ]. In a novel object retrieval task in which rats had to cross an unsafe, risky zone (filled with water) to be able to access, interact with and retrieve hidden novel objects, adolescent MS rats (pooled group including both sexes) exhibited reduced latencies to cross the risky zone and reach the platform containing novel objects, took less time to retrieve novel objects, and retrieved more objects than controls [ 124 ].…”

Addictive and other mental disorders: a call for a standardized definition of dual disorders

“…In addition, and similar to addictive disorders, the prevalence and severity of a DD is also linked to the early onset of the disorder [29,64], befitting the model of developmental disorders that often begin during late childhood and adolescence and may present with different phenotypes, whether addiction-related or other personality traits, such as disorganized attachment [65], impulsiveness [66], etc. Our growing understanding of the many ways in which environmental factors, such as trauma and early-life stress [67,68] or sleep deficits [69,70], can perturb brain development and function and increase the risk of addictive and/or other mental disorders, offers additional compelling arguments towards an improved explanation of the complex pathophysiology of DDs [71].…”