Improving Exposure Therapy: Rationale and Design of an International Consortium.

The Exposure Therapy Consortium (ETC) was established to advance the science and practice of exposure therapy. To encourage participation from researchers and clinicians, this article describes the organizational structure and activities of the ETC. Initial research working group experiences and a proof-of-principle study underscore the potential of team science and larger-scale collaborative research in this area. Clinical working groups have begun to identify opportunities to enhance access to helpful resources for implementing exposure therapy effectively. This article discusses directions for expanding the consortium's activities and its impact on a global scale.

The effects of diazepam on fear extinction in nulliparous and primiparous female rats.

Benzodiazepines undermine the success of exposure therapy in humans with anxiety disorders, and impair the long-term memory of fear extinction (the laboratory basis of exposure therapy) in rodents. However, most rodent studies on fear extinction and benzodiazepines have been conducted in male rodents. In female rodents, the estrous cycle influences the consolidation of fear extinction memories and sensitivity to benzodiazepines. In addition, pregnancy leads to long-term changes in the neurobiological, hormonal, and behavioural features of fear extinction, as well as the responsivity to benzodiazepines. Therefore, the present experiments examined the impact of benzodiazepines on fear extinction in female rats with and without reproductive experience. Age-matched nulliparous (no reproductive experience) and primiparous (one prior reproductive experience; tested one-month post-weaning) rats received fear conditioning to a discrete cue. The next day, rats were administered the benzodiazepine diazepam (2 mg/kg, s.c), or vehicle, prior to or immediately after extinction training. Rats were then tested the next day, drug free, for extinction retention. Similar to previous findings in males, diazepam impaired extinction retention in both nulliparous and primiparous rats when administered either pre- or post-extinction training. These findings may have potential clinical implications as they suggest that benzodiazepine use in conjunction with exposure therapy may undermine long-term treatment success in women with and without reproductive experience, although this remains to be tested in human populations. Moreover, these findings are theoretically important when considered in light of previous studies showing dissociable mechanisms of fear extinction in females pre- versus post-pregnancy.

Dissociable role of the basolateral complex of the amygdala in the acquisition and extinction of conditioned fear following reproductive experience in female rats.

In female rats and humans, reproductive experience (i.e., pregnancy) alters the behavioral, hormonal and molecular substrates of fear extinction. Here, we assessed whether the role of a central neural substrate of fear extinction, the basolateral amygdala (BLA), also changes following reproductive experience. Nulliparous (virgin) and primiparous (one prior pregnancy) female rats received infusions of the GABAA agonist, muscimol, to temporarily inactivate the BLA prior to fear conditioning or extinction training. In follow up experiments, the BLA was also inactivated immediately after extinction training. BLA inactivation impaired the acquisition and expression of conditioned fear in both nulliparous and primiparous rats. In nulliparous rats, BLA inactivation prior to or immediately after extinction training impaired extinction retention. In contrast, in primiparous rats, BLA inactivation prior to or immediately after extinction training did not impair extinction retention, despite suppressing freezing during extinction training. These results suggest that, consistent with past findings in males, the BLA is a central component of the neural circuitry of fear acquisition and its extinction in virgin female rats. However, after pregnancy, female rats no longer depend on the BLA to extinguish fear, despite requiring the BLA to acquire conditioned fear. Given that fear extinction forms the basis of exposure therapy for anxiety disorders in humans, the present findings may have clinical implications. To improve the efficacy of exposure therapy for anxiety disorders, we may need to target different mechanisms in females dependent on their reproductive history.

Reproductive experience alters the effects of diazepam and fluoxetine on anxiety-like behaviour, fear extinction, and corticosterone levels in female rats.

OVERVIEW: Reproductive experience (pregnancy and motherhood) leads to long-term changes in the neurobiological and hormonal features of anxiety in rats and humans. The aim of this study was to examine whether reproductive experience alters the effects of two pharmacological treatments for anxiety, a benzodiazepine (diazepam) and a selective serotonin reuptake inhibitor (fluoxetine), on animal models of anxiety. METHODS: In Experiment 1, virgin (n = 47) and age-matched mother (n = 50) rats at 1-month post-weaning were injected with diazepam (1.3 mg/kg or 1.7 mg/kg, i.p.) or vehicle, in the proestrus (high estradiol/progesterone/allopregnanolone) or metestrus (low estradiol/progesterone/allopregnanolone) phase of the estrous cycle 30 min prior to the elevated plus maze (EPM). In Experiment 2, virgin (n = 25) and mother rats (n = 20) were administered fluoxetine (10 mg/kg) or vehicle for 2 weeks prior to being tested on a Pavlovian fear conditioning and extinction protocol, and the EPM. RESULTS: Replicating past research, in virgin rats, the low dose of diazepam produced anxiolytic-like effects in proestrus, but only the high dose was anxiolytic-like in metestrus. In contrast, in mother rats, both doses of diazepam were anxiolytic-like irrespective of estrous phase. Fluoxetine produced anxiogenic-like effects in virgin rats during fear extinction and the EPM, but had no behavioural effects in mothers. In contrast, fluoxetine increased plasma corticosterone levels measured 30-min post-EPM in mothers, but not virgin rats. CONCLUSIONS: Reproductive experience alters the dose responsivity and efficacy of common anti-anxiety medications in female rats. These findings highlight the importance of considering reproductive status in studies on anxiety and its treatment.

The relationship between salivary Fibroblast Growth Factor-2 and cortisol reactivity and psychological outcomes prior to and during the COVID-19 pandemic.

Background: Fibroblast growth factor-2 (FGF2) is a biomarker that is associated with depression, anxiety and stress in rodents. In humans, we have previously demonstrated that salivary FGF2 increased following stress in a similar pattern to cortisol, and FGF2 (but not cortisol) reactivity predicted repetitive negative thinking, a transdiagnostic risk factor for mental illness. The current study assessed the relationship between FGF2, cortisol, and mental health before and during the COVID-19 pandemic. Methods: We employed a longitudinal correlational design using a convenience sample. We assessed whether FGF2 and cortisol reactivity following the Trier Social Stress Task (TSST) were associated with DASS-21 depression, anxiety and stress, measured at the time of the TSST in 2019-20 (n = 87; time 1), and then again in May 2020 during the first wave of COVID-19 in Sydney (n = 34 of the original sample; time 2). Results: FGF2 reactivity (but not absolute FGF2 levels) at time 1 predicted depression, anxiety, and stress across timepoints. Cortisol reactivity at time 1 was associated with stress over timepoints, and absolute cortisol levels were associated with depression across timepoints. Limitations: The sample was comprised of mostly healthy participants from a student population, and there was high attrition between timepoints. The outcomes need to be replicated in larger, more diverse, samples. Conclusions: FGF2 and cortisol may be uniquely predictive of mental health outcomes in healthy samples, potentially allowing for early identification of at-risk individuals.

The impact of the ovarian cycle on anxiety, allopregnanolone, and corticotropin releasing hormone changes after motherhood in female rats and women.

Fluctuations in ovarian steroids across the estrous and menstrual cycle in female rats and women, respectively, are associated with changes in anxiety. Pregnancy causes long-term changes to ovarian hormone release, yet research on estrous- and menstrual-related changes in anxiety has focused on reproductively inexperienced females. Therefore, this study assessed whether the impact of estrous and menstrual cycles on anxiety differs pre- versus post-motherhood in female rats (n = 32) and a community sample of women (n = 63). Estrous cycle phase altered anxiety-like behavior in virgin rats, but had no effect in age-matched mother rats tested 1-month post-weaning. In humans, menstrual cycle phase was associated with ecological momentary assessed anxiety and mood in non-mothers, but not mothers; although, the menstrual cycle × reproductive status interaction for anxiety, but not mood, was rendered non-significant with age and cycle length as covariates. These findings suggest that changes in anxiety coincident with cycling hormones is an evolutionarily conserved feature of the estrous and menstrual cycle in rats and women, which is mitigated following motherhood in both species. We identified several potential mechanisms for the observed dissociation in estrous cycle effects on anxiety. Compared to virgin rats, mother rats had a lower peak and blunted decline in circulating allopregnanolone during proestrus, upregulated GABAA receptor subunit (α1, α2, α5, α4, ß2) mRNA in the ventral hippocampus, and altered corticotropin-releasing hormone mRNA across the estrous cycle in the basolateral amygdala. Together, these findings suggest that the mechanisms underlying anxiety regulation undergo fundamental transformation following pregnancy in female rats and humans.

Female rodents are not more variable than male rodents: A meta-analysis of preclinical studies of fear and anxiety.

Recent meta-analyses have demonstrated that data from female rodents, tested without regard for estrous stage, is no more variable than male data across a range of traits. Nonetheless, widespread use of male-only samples persists in preclinical studies of anxiety disorders, despite this condition being twice more prevalent amongst women relative to men. We conducted a meta-analysis of over 4900 data points obtained from 263 articles assessing behavioural measures of fear and anxiety in rodents. We found no evidence for greater female variability on any measure. Overall, males had greater variability than unstaged females, which was predominantly driven by studies of learned fear. Compared to unstaged females, staged, but not ovariectomised, females showed reduced variability. Experiments using individual housing and rats were associated with greater variability relative to those using group housing and mice; these effects were not moderated by sex. These results illustrate that the estrous cycle does not inflate variability in females beyond that of males, despite being a female-specific modulator of fear and anxiety behaviour.

The relative efficacy and efficiency of single- and multi-session exposure therapies for specific phobia: A meta-analysis.

Exposure therapy is the preferred treatment for specific phobia (SP), with evidence supporting its efficacy whether delivered over multiple sessions or as a single session, such as One-Session Treatment. In this meta-analysis, we compared the efficiency and effectiveness of single- and multi-session exposure for SP. PsycINFO, Embase, MEDLINE, and Cochrane were systematically searched for peer-reviewed articles reporting the effects of multi-session (k = 30) and/or single-session (k = 55) in vivo exposure on SP symptoms in clinical populations (n = 1758 participants). A random-effects model was used to synthesise and compare the pre-post treatment effects (Hedges' g) on approach behaviour and self-reported SP symptoms. Mean total treatment time was significantly longer for multi-session exposure than for single-session. There were no significant differences in the pooled effect sizes of single-session and multi-session exposure at post-treatment and follow-up assessments; effect sizes were large for all outcomes. Phobia subtype significantly moderated the effect size for both treatment approaches, although the direction of association differed according to the outcome measures. Results suggest no evidence for differences in the effectiveness of single- and multi-session exposure, but single-session is more time efficient. These outcomes suggest that policies to facilitate access to single-session exposure would be beneficial.

What Pre-clinical Rat Models Can Tell Us About Anxiety Across the Menstrual Cycle in Healthy and Clinically Anxious Humans.

PURPOSE OF REVIEW: Anxiety symptoms increase during the peri-menstrual phase of the menstrual cycle in people with anxiety disorders. Whether this reflects a heightened variant of normal menstrual-related changes in psychological states experienced by healthy (i.e. non-anxious) people is unknown. Moreover, menstrual-related change in anxiety symptoms is a poorly understood phenomenon, highlighting a need for pre-clinical models to aid mechanistic discovery. Here, we review recent evidence for menstrual effects on anxiety-like features in healthy humans as a counterpart to recent reviews that have focused on clinically anxious populations. We appraise the utility of rodent models to identify mechanisms of menstrual effects on anxiety and offer suggestions to harmonise methodological practices across species to advance knowledge in this field. RECENT FINDINGS: Consistent with reports in clinical populations, some evidence indicates anxiety symptoms increase during the peri-menstrual period in healthy people, although null results have been reported, and these effects are heterogeneous across studies and individuals. Studies in rats show robust increases in anxiety during analogous phases of the oestrous cycle. Studies in female rats are useful to identify the evolutionarily conserved biological mechanisms of menstrual-related changes in anxiety. Future experimental approaches in rats should model the heterogeneity observed in human studies to increase alignment across species and advance understanding of the individual factors that increase the propensity to experience menstrual-related changes in anxiety.

The impact of hormonal contraceptives on anxiety treatments: From preclinical models to clinical settings.

Exposure therapy is a central component of the first-line treatment for anxiety disorders, a common mental health condition that is twice as prevalent in women relative to men. A key underlying mechanism of exposure therapy is fear extinction, which is an active learning process supported by a neural circuitry that is highly regulated by ovarian hormones. This review synthesises research examining the impact of hormonal contraceptives on laboratory fear extinction tasks in female rats and women, and on exposure therapy in women with anxiety disorders. The evidence indicates that hormonal contraceptives have a detrimental impact on fear extinction and exposure therapy that is consistent across species, and from laboratory to clinical settings. Candidate pathways by which hormonal contraceptives impede fear extinction and exposure therapy include suppression of endogenous ovarian hormones and glucocorticoids, and downregulation of signalling pathways that support extinction learning. Key areas of focus for future research are discussed.

The Association Between Salivary FGF2 and Physiological and Psychological Components of the Human Stress Response.

Background: Fibroblast Growth Factor 2 (FGF2) is a neurotrophic protein that has been implicated as a biomarker for anxiety and depressive disorders, which comprise a significant component of the global burden of disease. Research using rodents has indicated that FGF2 is part of the stress response, but whether this translates to humans has yet to be investigated. In this study, we aimed to explore the potential role of FGF2 in the human stress response by examining its association with physiological and psychological processes during and following the Trier Social Stress Test (TSST). Methods: Participants in the active stress experiment (N = 87) underwent the TSST, provided saliva samples to obtain levels of cortisol and FGF2, and reported on post-event rumination related to the TSST task over the following week. Participants in the no-stress experiment (N = 25) provided saliva samples for measurement of FGF2 and cortisol across a corresponding time period. Results: Salivary FGF2 levels changed after the TSST and were associated with the pattern of change in salivary cortisol. Cortisol responses in the active stress condition were blunted in females (relative to males), however, sex did not interact with any other effect. FGF2 reactivity (ie, the magnitude of change over time) was not correlated with cortisol reactivity. Lower FGF2 reactivity following the TSST, but not overall FGF2 levels, or cortisol, was associated with higher fear of negative evaluation, repetitive negative thinking and post-event processing, as well as repetitive negative thinking in the week following the TSST. Participants in the no-stress experiment showed a decrease in cortisol, yet no change in their FGF2 levels. Conclusion: These findings suggest that FGF2 is involved in the human stress response and higher levels of FGF2 reactivity may be associated with protective cognitive processes following stress exposure.

The relationship between repetitive negative thinking, sleep disturbance, and subjective fatigue in women with Generalized Anxiety Disorder.

OBJECTIVES: Fatigue is a prominent symptom of Generalized Anxiety Disorder (GAD). However, the pathways contributing to elevated fatigue in GAD are poorly understood. Sleep disturbance, also prominent in GAD, only partially explains elevated fatigue in GAD. Repetitive negative thinking (RNT) is a cognitive feature of both GAD and sleep disturbance, and RNT has recently also been associated with elevated fatigue. Therefore, this study assessed whether elevated fatigue in GAD is accounted for by a combination of sleep quality and RNT. DESIGN: Between-group, correlational design in 64 primarily university-educated women with and without a GAD diagnosis. METHODS: Women completed self-report questionnaires assessing RNT experienced in the past few days, previous night's sleep quality, and current physical and mental fatigue. Hierarchical linear regressions were conducted to assess whether the relationship between GAD status and fatigue is accounted for by RNT and sleep quality. RESULTS: Women with GAD reported lower sleep quality, and higher RNT and physical and mental fatigue, compared to women without GAD. Sleep quality partly accounted for group differences in both types of fatigue (ß's > -0.4), whereas RNT fully accounted for group differences in both types of fatigue (ß's > 0.29). The relationship between RNT and both types of fatigue was fully accounted for by sleep quality (ß's > -0.39). CONCLUSIONS: These findings indicate that heightened RNT amongst women with GAD may be associated with elevated physical and mental fatigue via its detrimental effects on sleep quality. Interventions that reduce RNT may help to alleviate fatigue symptoms in women with GAD. PRACTITIONER POINTS: Women with Generalized Anxiety Disorder (GAD) have elevated fatigue and repetitive negative thinking (RNT), and poorer self-reported sleep quality, relative to women without GAD. Whereas sleep quality only partially accounts for elevated fatigue in GAD, RNT fully accounts for elevated fatigue, and the relationship between RNT and fatigue is fully accounted for by sleep quality. These findings provide novel evidence that women with GAD may have elevated fatigue because of the detrimental effects of RNT on sleep. These findings suggest that targeting RNT in treatment for GAD may help to reduce fatigue in GAD, by improving sleep quality.

Symptom fluctuation over the menstrual cycle in anxiety disorders, PTSD, and OCD: a systematic review.

Anxiety disorders are more prevalent and severe in women than men. Extant research suggests that the menstrual cycle modulates the severity and expression of anxiety symptoms across a range of disorders. The aims of this systematic review were to synthesise the existing literature investigating menstrual phase-related fluctuations in symptoms of anxiety disorders, and related conditions PTSD and OCD, in menstruating women, and to evaluate the methodologies used. PsycINFO and PubMed were searched through to April 2021 for studies that measured and compared symptoms of a diagnosed anxiety disorder, PTSD, or OCD, between at least two menstrual phases. Fourteen studies meeting inclusion criteria were identified. The review revealed evidence for exacerbation of a broad range of symptoms in panic disorder, PTSD, social anxiety disorder, and generalised anxiety disorder, around the weeks prior to and post menses onset, coincident with elevated but declining ovarian hormones, and low hormone levels, respectively. Effects were heterogenous between individuals and different symptom types. Key methodological weaknesses included sub-optimal and inconsistent means of defining and identifying menstrual phases, low sample representativeness, and small sample sizes. Menstrual fluctuations in anxiety symptoms appear to be a feature of anxiety disorders, PTSD, and OCD, but likely only occur in a subset of women. Future research in this field could better manage and account for such heterogeneity by using group-based trajectory modelling in larger sample sizes and using pre-screening to recruit women with known histories of menstrual fluctuation in anxiety symptoms.

Mind's eye: The impact of spider presence and cognitive therapy on size estimation biases in spider phobia.

The present study assessed the circumstances under which size estimation biases in spider phobia occur, and whether such biases are modifiable by treatment. Women with (n = 67) and without (n = 33) spider phobia approached a spider during a behavioral approach test (BAT). They provided size estimates of the spider both during and shortly after the BAT (with the spider in view, or not in view, respectively). Phobic women then received cognitive therapy or a placebo treatment and one week later they underwent a second BAT and provided size estimates of the same spider during and after the BAT. Phobic women reported larger size estimates than non-phobic women after, but not during, the BAT. Size estimates after, but not during, the BAT correlated with self-reported fear but not avoidance. Size estimates after, but not during, the BAT reduced from the first to second BAT in phobic women; an effect evident in both the cognitive therapy and placebo treatment conditions. Changes in size estimates were not associated with treatment-induced reductions in fear or avoidance. These results suggest that estimation biases in spider phobia are likely driven by non-perceptual processes. The clinical utility of size estimation measures is discussed.

Subjective sleep quality and characteristics across the menstrual cycle in women with and without Generalized Anxiety Disorder.

OBJECTIVE: Past studies have found that various psychiatric symptoms fluctuate over the menstrual cycle. Sleep disturbance is a transdiagnostic feature of psychiatric conditions and is associated with several symptoms that exhibit menstrual fluctuations. Although some evidence indicates that subjective sleep quality changes over the menstrual cycle in healthy women, no studies have investigated whether sleep fluctuates over the menstrual cycle in psychiatric populations, other than premenstrual dysphoric disorder. METHODS: The present study used a mixed between- within-groups design to compare self-reported sleep characteristics (sleep onset latency, number and duration of night-time awakenings, and total sleep time), sleep quality, insomnia symptoms, and daytime sleepiness in women with (n = 31) and without (n = 32) generalized anxiety disorder (GAD) at two time points within a single menstrual cycle - the early-follicular (low ovarian hormones) and mid-luteal (high ovarian hormones) phases. RESULTS: Women with GAD reported lower sleep quality, more insomnia symptoms, and more daytime sleepiness (ηp2 = 0.13-0.14), but comparable sleep characteristics, compared to women without GAD. In both groups, sleep variables remained stable over the menstrual phases examined. Within-person changes in estradiol and progesterone between the two menstrual phases were mostly not associated with within-person changes in sleep variables, except that larger increases in estradiol were associated with a reduction in the number of night-time awakenings from the early-follicular to mid-luteal phases (ß = -0.26). CONCLUSION: These findings indicate that subjective sleep disturbance, unlike other psychiatric symptoms, may not be modulated by the menstrual cycle and ovarian hormones during the phases examined in this study.

It's all about who you know: Memory retention of a rat's cagemates during infancy negatively predicts adulthood hippocampal FGF2.

Recent research has demonstrated that individual differences in infant fear memory positively predict adulthood anxiety-like behavior and conditioned fear expression. However, the physiological mechanisms underlying this relationship and the effect of environmental (e.g., social) influences on the stability of this relationship have not been explored. In the present study, we examined whether individual differences in infant fear memory predict levels of endogenous fibroblast growth factor-2 (FGF2; a biomarker of fear/anxiety) in adulthood, and whether the mean memory retention of a rat's cagemates predicts conditioned fear expression and FGF2 in adulthood. We conditioned infant rats to associate a white noise with shock, and tested their memory of the association 1 week later. They were then weaned and randomly assigned to cage/cagemates. In adulthood, rats received weak context conditioning (i.e., a single shock) and were tested for fear of the context the following day. Rats were then euthanized and their brains extracted to measure levels of hippocampal FGF2 protein. Across 2 experiments, an individual rat's fear memory during infancy positively predicted their own fear expression in adulthood, but the mean memory retention of their cagemates did not predict fear expression. In contrast, the mean memory retention of a rat's cagemates during infancy negatively predicted hippocampal FGF2 protein in adulthood, but an individual rat's memory retention did not predict their own levels of FGF2. These data support the idea that variations in the fearfulness of a rat's cagemates predict individual differences on physiological measures in adulthood.

Gender Differences in Adolescent Sleep Disturbance and Treatment Response to Smartphone App-Delivered Cognitive Behavioral Therapy for Insomnia: Exploratory Study.

BACKGROUND: Insomnia and sleep disturbance are pervasive and debilitating conditions affecting up to 40% of adolescents. Women and girls are at greater risk of insomnia, yet differences in treatment responsiveness between genders have not been adequately investigated. Additionally, while women report greater symptom severity and burden of illness than men, this discrepancy requires further examination in adolescents. OBJECTIVE: The purpose of this study was to examine gender differences in sleep symptom profiles and treatment response in adolescents. METHODS: Digital cognitive behavioral therapy for insomnia (CBT-I) treatment responsiveness, as indexed by changes in Insomnia Severity Index (ISI) and Global Pittsburgh Sleep Quality Index (PSQI) scores, was compared in boys and girls (aged 12-16 years; N=49) who participated in a pilot evaluation of the Sleep Ninja smartphone app. Gender differences in self-reported baseline insomnia symptom severity (ISI), sleep quality (PSQI), and sleep characteristics derived from sleep diaries were also examined. RESULTS: Compared with boys, we found that girls reported greater symptom severity (P=.04) and nighttime wakefulness (P=.01 and P=.04) and reduced sleep duration (P=.02) and efficiency (P=.03), but not poorer sleep quality (P=.07), more nighttime awakenings (P=.16), or longer time to get to sleep (P=.21). However, gender differences in symptom severity and sleep duration were accounted for by boys being marginally younger in age. Treatment response to CBT-I was equivalent between boys and girls when comparing reductions in symptom severity (P=.32); there was a trend showing gender differences in improvements in sleep quality, but this was not statistically significant (P=.07). CONCLUSIONS: These results demonstrate the presence of gender differences in insomnia symptoms and severity in adolescents and suggest further research is required to understand gender differences in insomnia symptom profiles to inform the development of gender-specific digital interventions delivered to adolescents.

Maternal Experience Does Not Predict Fear Extinction and Anxiety-Like Behaviour in Primiparous Rats Post-weaning.

Reproductive experience leads to long-lasting changes in anxiety-like behaviour and fear extinction, the laboratory model of exposure therapy for anxiety disorders. For example, fear extinction is influenced by estrous cycle in nulliparous (no reproductive experience) female rats, but this effect is abolished in primiparous (one reproductive experience) females. It is unclear whether such changes are driven by pregnancy, maternal experience of caring for offspring during the postpartum period, or a combination of both experiences. The present study sought to determine the influence of maternal experience (i.e., exposure to pups and mother-pup interactions) on fear extinction in primiparous rats. In Experiment 1, we tested whether pup exposure is necessary to mitigate estrous effects on fear extinction in primiparous rats. Age-matched nulliparous rats, primiparous rats, and primiparous rats who experienced pregnancy but not pup exposure, underwent fear conditioning on day 1 (2 months post-parturition), extinction training during proestrus (high sex hormones) or metestrus (low sex hormones) on day 2, and extinction recall on day 3. Replicating past research, nulliparous rats showed impaired extinction recall when they were extinguished during metestrus compared to proestrus. In contrast, primiparous rats with and without pup exposure showed comparable extinction recall irrespective of estrous phase. In Experiment 2, we assessed whether naturally-occurring variation in mother-pup interactions predict future fear extinction performance and anxiety-like behaviour. During the first week of lactation, primiparous rats were measured for maternal behaviours toward pups. Primiparous rats were then tested on the light-dark box and elevated plus maze to measure anxiety-like behaviour and underwent a fear extinction protocol 1 month post-weaning. We found no significant correlations between maternal behaviour and fear extinction outcomes or anxiety-like behaviour. Our findings suggest that pregnancy, not maternal experience, mitigates the impact of estrous cycle on fear extinction. In addition, natural variation in maternal experience does not appear to contribute to variability in future fear extinction outcomes or anxiety-like behaviour in primiparous rats.