High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults

Abstract Rationale The combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centered in male rodents, traditionally excluding females from these analyses. Objectives To ascertain the behavioral and neurochemical consequences of adolescent cocaine exposure when the combination of several risk factors is present (female, early-life stress). Methods Whole litters of Sprague–Dawley rats were exposed to maternal deprivation for 24 h on postnatal day (PND) 9. Cocaine was administered in adolescence (15 mg/kg/day, i.p., PND 33–39). Negative affect was assessed by several behavioral tests (forced swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal cell fate markers were evaluated by western blot (FADD, Bax, cytochrome c) or immunohistochemistry (Ki-67; cell proliferation). Results Maternal deprivation is a suitable model of psychiatric vulnerability in which to study the impact of adolescent cocaine in female rats. While adolescent cocaine did not alter affective-like behavior during adolescence, a pro-depressive–like state emerged during adulthood, exclusively in rats re-exposed to cocaine during abstinence. FADD regulation by cocaine in early-life stressed female rats might contribute to certain hippocampal neuroadaptations with some significance to the observed induced negative affect. Conclusions Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress, highlighting the risk of early drug initiation during adolescence for the emergence of negative reinforcement during abstinence likely driving cocaine addiction vulnerability, also in female rats.

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Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.766505 ◽

2021 ◽

Vol 15 ◽

Author(s):

Dayan Knox ◽

Stephanie A. Stout-Oswald ◽

Melissa Tan ◽

Sophie A. George ◽

Israel Liberzon

Keyword(s):

Risk Factors ◽

Sex Differences ◽

Animal Models ◽

Traumatic Stress ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Female Rats ◽

Male Rats

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.

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Early Life Stress and Sleep Restriction as Risk Factors in PTSD: An Integrative Pre-Clinical Approach

10.21236/ada567825 ◽

2012 ◽

Author(s):

Gal Richter-Levin

Keyword(s):

Risk Factors ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Sleep Restriction ◽

Clinical Approach

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HDAC1 links early life stress to schizophrenia-like phenotypes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613842114 ◽

2017 ◽

Vol 114 (23) ◽

pp. E4686-E4694 ◽

Cited By ~ 37

Author(s):

Sanaz Bahari-Javan ◽

Hristo Varbanov ◽

Rashi Halder ◽

Eva Benito ◽

Lalit Kaurani ◽

...

Keyword(s):

Risk Factors ◽

Dna Methylation ◽

Prefrontal Cortex ◽

Histone Deacetylase ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Blood Samples ◽

Histone Deacetylase 1 ◽

Disease Phenotypes

Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.

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