scholarly journals Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Ray R. Denny ◽  
Krista L. Connelly ◽  
Marco G. Ghilotti ◽  
Joseph J. Meissler ◽  
Daohai Yu ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Alcohol Use ◽  
Neuropeptide Y ◽  
Traumatic Stress ◽  
Alcohol Use Disorder ◽  
Ethanol Consumption ◽  
Female Rats ◽  
Stress Exposure ◽  
Ethanol Drinking ◽  
Artificial Intelligence Algorithm

Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.

Post-traumatic stress disorder and alcohol use disorder

2002 ◽  
Vol 8 (2) ◽  
pp. 55-61 ◽  
Author(s):  
I. Roncevic-Grzeta ◽  
Lj. Moro ◽  
T. Franciskovic ◽  
T. Ruzic ◽  
B. Smokvina ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Alcohol Use Disorder ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Post Traumatic

scholarly journals Investigating the sex-specific effects of socialization on voluntary ethanol self-administration in rats using the vapor chamber

2020 ◽  
Author(s):  
Christopher D. Walker ◽  
Hannah G. Sexton ◽  
Mary-Louise Risher
Keyword(s):  
Body Weight ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Adult Male ◽  
Ethanol Vapor ◽  
Ethanol Consumption ◽  
Female Rats ◽  
Male Rats ◽  
Self Administration ◽  
Nose Poke

ABSTRACTIntroductionPeer interactions are a crucial part of social and personal development, particularly during adolescence. Adolescence is characterized as a transitional developmental period between childhood and adulthood that is often associated with increased freedom, self-exploration, and novel experiences that are frequently peer-influenced. Due to newfound independence, there is a higher prevalence of alcohol consumption, which is in part due to the heightened social facilitating and rewarding effects of alcohol. Previous work shows that males and females who consume excessive alcohol during adolescence are at an increased risk of developing an alcohol use disorder (AUD) later in life. However, the contributions of social interaction and sexual dimorphism in alcohol consumption, two driving factors that influence AUD risk, are not fully understood. Many current rat models used to study the characteristics of alcohol use and the emergence of AUD coerce the animals into consuming liquid ethanol by the addition of a sweetener, which has been proven to confound results in adolescent rats. Here we use a novel self-administration ethanol vapor system to investigate the sexual dimorphic nature of socially facilitated ethanol consumption without the addition of sweeteners.MethodsAdolescent and adult male and female Sprague-Dawley rats underwent a novel voluntary chronic intermittent self-administration ethanol vapor paradigm. Nose poke-initiated self-administration vapor chambers (La Jolla Alcohol Research, Inc.) administered 20mg/L of vaporized ethanol or air (control) into the chamber in response to each individual nose poke. Beginning on postnatal day (PND) 30 or PND70, animals were placed in vapor chambers for 4 hours every other day for a total of 40 sessions. All animals underwent 10 sessions with their cagemate (social access) followed by 10 sessions in isolation (isolated access), a 10 day forced abstinence period, 10 sessions in isolation (isolated access), and 10 sessions with their cagemate (social access).ResultsFemale rats consumed more alcohol per body weight than age-matched males, while male rats increased ethanol preference over sessions regardless of age. In addition, all rats regardless of sex or age consumed more ethanol per body weight during the first social access session than during the subsequent isolated access sessions. Interestingly, there was an increase in ethanol consumption in adult male and females during the second social access session compared to the previous isolated access session that was not observed in either adolescent groups.ConclusionThese data demonstrate that female and male rats, regardless of age, are vulnerable to socially facilitated ethanol consumption. This is consistent with human data showing that increased levels of alcohol consumption among adolescents and young adults is associated with high levels of alcohol use within their social group (Sudhinaraset, Wigglesworth, & Takeuchi, 2016). However, only male rats demonstrate escalation across sessions. This may indicate that male rats are more vulnerable to escalated drinking and the emergence of ethanol dependence compared to females regardless of peer interaction. These data demonstrate that the self-administration ethanol vapor system is an effective alternative to other methods of voluntary ethanol administration for investigating factors that contribute to alcohol use and escalation.

scholarly journals Juvenile exposure to acute traumatic stress leads to long-lasting alterations in grey matter myelination in adult female but not male rats

2020 ◽  
Author(s):  
Jocelyn M Breton ◽  
Matthew Barraza ◽  
Kelsey Y Hu ◽  
Samantha Joy Frias ◽  
Kimberly L.P. Long ◽  
...  
Keyword(s):  
Traumatic Stress ◽  
Grey Matter ◽  
Acute Stress ◽  
Brain Regions ◽  
Adult Brain ◽  
Female Rats ◽  
Male Rats ◽  
Stress Exposure ◽  
Corticosterone Release

Stress early in life can have a major impact on brain development, and there is increasing evidence that childhood stress confers vulnerability for later developing psychiatric disorders. In particular, during peri-adolescence, brain regions crucial for emotional regulation, such as the prefrontal cortex (PFC), amygdala (AMY) and hippocampus (HPC), are still developing and are highly sensitive to stress. Changes in myelin levels have been implicated in mental illnesses and stress effects on myelin and oligodendrocytes (OLs) are beginning to be explored as a novel and underappreciated mechanism underlying psychopathologies. Yet there is little research on the effects of acute stress on myelin during peri-adolescence, and even less work exploring sex-differences. Here, we used a rodent model to test the hypothesis that exposure to acute traumatic stress as a juvenile would induce changes in OLs and myelin content across limbic brain regions. Male and female juvenile rats underwent three hours of restraint stress with exposure to a predator odor on postnatal day (p) 28. Acute stress induced a physiological response, increasing corticosterone release and reducing weight gain in stress-exposed animals. Brain sections containing the PFC, AMY and HPC were taken either in adolescence (p40), or in adulthood (p95) and stained for markers of OLs and myelin. We found that acute stress induced sex-specific changes in grey matter (GM) myelination and OLs in both the short- and long-term. Exposure to a single stressor as a juvenile increased GM myelin content in the AMY and HPC in p40 males, compared to the respective control group. At p40, corticosterone release during stress exposure was also positively correlated with GM myelin content in the AMY of male rats. Single exposure to juvenile stress also led to long-term effects exclusively in female rats. Compared to controls, stress-exposed females showed reduced GM myelin content in all three brain regions. Acute stress exposure decreased PFC and HPC OL density in p40 females, perhaps contributing towards this observed long-term decrease in myelin content. Overall, our findings suggest that the juvenile brain is vulnerable to exposure to a brief severe stressor. Exposure to a single short traumatic event during peri-adolescence produces long-lasting changes in GM myelin content in the adult brain of female, but not male, rats. These findings highlight myelin plasticity as a potential contributor to sex-specific sensitivity to perturbation during a critical window of development.

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