Sex differences in acute early life stress-enhanced fear learning in adult rats.

Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.

Gonadal hormones and sex chromosome complement differentially contribute to ethanol intake, preference, and relapse-like behaviour in four core genotypes mice.

Alcohol use and high-risk alcohol drinking behaviours among women are rapidly rising. In rodent models, females typically consume more ethanol (EtOH) than males. Here, we used the four core genotypes (FCG) mouse model to investigate the influence of gonadal hormones and sex chromosome complement on EtOH drinking behaviours. FCG mice were given access to escalating concentrations of EtOH in a two-bottle, 24-h continuous access drinking paradigm to assess consumption and preference. Relapse-like behaviour was measured by assessing escalated intake following repeated cycles of deprivation and re-exposure. Twenty-four-hour EtOH consumption was greater in mice with ovaries (Sry-), relative to those with testes, and in mice with the XX chromosome complement, relative to those with XY sex chromosomes. EtOH preference was higher in XX versus XY mice. For both consumption and preference, the influences of the Sry gene and sex chromosomes were concentration dependent. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). Mice with ovaries (Sry- FCG mice and C57BL/6J females) were also found to consume more water than mice with testes. These results demonstrate that aspects of EtOH drinking behaviour may be independently regulated by sex hormones and chromosomes and inform our understanding of the neurobiological mechanisms which contribute to EtOH dependence in male and female mice. Future investigation of the contribution of sex chromosomes to EtOH drinking behaviours is warranted. We used the FCG mouse model to investigate the influence of gonadal hormones and sex chromosome complement on EtOH drinking behaviours, including the alcohol deprivation effect. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). These results demonstrate that aspects of EtOH drinking behaviour may be independently regulated by sex hormones and chromosomes.

Acute early life stress alters threat processing in adult rats.

Individuals diagnosed with stress-related psychiatric disorders in adulthood are likely to have experienced early life stress, suggesting that early adversity is an important vulnerability factor in the subsequent development of trauma- and anxiety-related psychiatric illness. It is important to develop animal models of psychiatric dysfunction to determine evident vulnerability considerations, potential biomarkers, and novel treatment avenues to improve the human condition. In our model of acute early life stress (aELS), 15 footshocks are delivered in a single session on postnatal day 17. The following experiments investigated the persistent impacts of our aELS procedure on stress-enhanced fear learning, anxiety-related behaviors, maintenance of fear, and resistance to extinction in adult male and female rats. The findings from these experiments demonstrate that our aELS procedure yields enhanced fear learning and increased anxiety. This enhanced fear is maintained over time, yet it extinguishes normally. Taken together, these results demonstrate that exposure to 15 footshocks during a single session early in life (postnatal day 17) recapitulates a number of important features of trauma- and anxiety-related disorder symptomatology, but not others. Future studies are needed to determine the persistent physiological phenotypes resulting from aELS and the neurobiological mechanisms that mediate these long-term changes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).