scholarly journals Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress

2021 ◽  
Author(s):  
Cristian Bis-Humbert ◽  
M. Julia García-Fuster
Keyword(s):  
Risk Factors ◽  
Negative Affect ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Maternal Deprivation ◽  
Female Rats ◽  
Suitable Model ◽  
The Impact ◽  
Early Drug

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.

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

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.

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

The effects of early‐life stress on dopamine system function in adolescent female rats

2017 ◽  
Vol 57 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Iwona Majcher‐Maślanka ◽  
Anna Solarz ◽  
Krzysztof Wędzony ◽  
Agnieszka Chocyk
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Adolescent Female ◽  
System Function ◽  
Dopamine System

scholarly journals Correction: N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0142228 ◽  
Author(s):  
Matteo M. Pusceddu ◽  
Sahar El Aidy ◽  
Fiona Crispie ◽  
Orla O’Sullivan ◽  
Paul Cotter ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Polyunsaturated Fatty Acids ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
The Impact

IMPACT OF EARLY LIFE STRESS ON ANTI-DEPRESSANT SENSITIVITY

2021 ◽  
pp. 123-132
Author(s):  
V.A. Vokina
Keyword(s):  
Open Field ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Anxiety Level ◽  
Male Rats ◽  
Porsolt Test ◽  
The Impact ◽  
Sexually Mature

Long-term consequences of impaired perinatal development are very significant. They appear during the neonatal period and in the first years of life, and persist during ontogenesis. There is little data on the impact of any prenatal factors on the sensitivity of a sexually mature organism to medications. The aim of the study is to assess the impact of early life stress on the development of individual antidepressant sensitivity. Materials and Methods. The authors conducted the experiments on sexually mature outbred male rats. To simulate the early life stress, a standard protocol was used. From the 2nd to 15th days of the postnatal period the pup rats were separated from their mother for 3 hours and kept in an incubator. The open-field test, Porsolt test and Sucrose consumption test were used to determine rat’s anxiety level as well as motor, orientation and exploratory activity at puberty. Then, for 14 days, the rats were intragastrically administered with a fluoxetine solution (10 mg/kg/daily), followed by their full examination. Statistical analysis of results was performed using the Mann-Whitney U-test to compare unrelated groups and Wilcoxon's test to compare related groups. Results. Fluoxetine did not have a pronounced antidepressant effect in animals that survived the early life stress. Such animals demonstrated passive floating during the Porsolt test, without any changes in immobility time. When testing in an open field, a sharp increase in the number of freezing behavior was observed, which was an indicator of an increased anxiety level in animals. Conclusion. The results obtained indicate that the long-term effects of neonatal stress may be associated with a change in antidepressant sensitivity or an increase in development of unwanted adverse reactions. Keywords: early life stress, depression, antidepressants, fluoxetine, rats. Отдаленные последствия нарушения перинатального развития весьма значительны и не только проявляются в период новорожденности и в первые годы жизни, но и сохраняются в период онтогенеза. Данные о влиянии каких-либо пренатальных факторов на чувствительность половозрелого организма к действию лекарственных веществ в доступной литературе представлены незначительно. Цель исследования – оценить роль стресса раннего периода жизни в формировании индивидуальной чувствительности к действию антидепрессантов. Материалы и методы. Эксперименты проведены на половозрелых беспородных крысах-самцах. Для моделирования стресса раннего периода жизни использовали стандартный протокол, подразумевающий отделение детенышей от матери со 2-го по 15-й дни постнатального периода на 3 ч в условиях инкубатора. В половозрелом возрасте проводили оценку уровня тревожности, двигательной и ориентировочно-исследовательской активности крыс в условиях теста открытого поля, теста Порсолта и теста «Потребление раствора сахарозы». Затем в течение 14 дней крысам внутрижелудочно вводили раствор флуоксетина (10 мг/кг/сут), после чего обследование повторяли в том же объеме. Статистический анализ результатов исследования проводили с использованием U-критерия Манна–Уитни для сравнения несвязанных групп и критерия Вилкоксона для сравнения связанных групп. Результаты. У животных, переживших стресс раннего периода жизни, флуоксетин не оказывал выраженного антидепрессантного действия. У данных животных в тесте Порсолта преобладало пассивное плавание, без изменения длительности иммобильности. При тестировании в открытом поле наблюдалось резкое повышение числа актов фризинга, что является показателем повышенного уровня тревожности у животных. Выводы. Полученные результаты свидетельствуют о том, что отдаленные последствия неонатального стресса могут быть связанны с изменением чувствительности к действию антидепрессантов или повышением риска развития нежелательных побочных реакций. Ключевые слова: стресс раннего периода жизни, депрессия, антидепрессанты, флуоксетин, крысы.

scholarly journals Maternal separation in rodents: a journey from gut to brain and nutritional perspectives

2019 ◽  
Vol 79 (1) ◽  
pp. 113-132 ◽  
Author(s):  
Marion Rincel ◽  
Muriel Darnaudéry
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Human Subjects ◽  
Early Life Stress ◽  
Long Term Effects ◽  
Early Life Adversity ◽  
Critical Window ◽  
Beneficial Impact ◽  
The Impact

The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut–brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut–brain axis. Further research is required to understand the complex mechanisms underlying gut–brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.

scholarly journals The Impact of COVID-19 on Adolescent Mental Health: Preliminary Findings From a Longitudinal Sample of Healthy and At-Risk Adolescents

2021 ◽  
Vol 9 ◽  
Author(s):  
Zsofia P. Cohen ◽  
Kelly T. Cosgrove ◽  
Danielle C. DeVille ◽  
Elisabeth Akeman ◽  
Manpreet K. Singh ◽  
...  
Keyword(s):  
Psychological Functioning ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Self Report ◽  
Depression And Anxiety ◽  
Mixed Effect ◽  
Symptoms Of Depression ◽  
The Impact ◽  
At Risk Adolescents

Background: The COVID-19 pandemic has brought on far-reaching consequences for adolescents. Adolescents with early life stress (ELS) may be at particular risk. We sought to examine how COVID-19 impacted psychological functioning in a sample of healthy and ELS-exposed adolescents during the pandemic.Methods: A total of 24 adolescents (15 healthy, nine ELS) completed self-report measures prior to and during the COVID-19 pandemic. The effect of COVID-19 on symptoms of depression and anxiety were explored using linear mixed-effect analyses.Results: With the onset of the pandemic, healthy but not ELS-exposed adolescents evidenced increased symptoms of depression and anxiety (ps < 0.05). Coping by talking with friends and prioritizing sleep had a protective effect against anxiety for healthy adolescents (t = −3.76, p = 0.002).Conclusions: On average, this study demonstrated large increases in depression and anxiety in adolescents who were healthy prior to the COVID-19 pandemic, while ELS-exposed adolescents evidenced high but stable symptoms over time.

scholarly journals Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

2020 ◽  
Vol 10 (7) ◽  
pp. 447 ◽  
Author(s):  
Héctor González-Pardo ◽  
Jorge L. Arias ◽  
Eneritz Gómez-Lázaro ◽  
Isabel López Taboada ◽  
Nélida M. Conejo
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Mitochondrial Function ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Dopamine Turnover ◽  
Mitochondrial Energy Metabolism ◽  
Brain Mitochondrial Function

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.

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