Abstract
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.
Highlights
Women are twice as likely to be diagnosed with an anxiety disorder compared to men [1], and they experience a greater symptom severity, burden of illness, and comorbidity between disorders [2]
The results of the current study demonstrate that maternal experience may not be necessary to alter the hormonal features of fear extinction following reproductive experience reported in past work and replicated here
Experiment 2 found no correlation between maternal care behaviours and fear extinction indices or anxiety-like behaviour on the light-dark box (LDB) or elevated plus maze (EPM) in primiparous rats
Summary
Women are twice as likely to be diagnosed with an anxiety disorder compared to men [1], and they experience a greater symptom severity, burden of illness, and comorbidity between disorders [2]. The vulnerability to develop an anxiety disorder fluctuates over the female reproductive lifespan with the greatest risk occurring during the postpartum time [3, 4]. Animal studies investigating the development and treatment of anxiety disorders have primarily been conducted in male rats [8], and the few studies that have included females have mostly used female rats without prior reproductive experience. This includes studies on fear extinction, which forms the laboratory basis of exposure therapy, a highly effective treatment for anxiety disorders [9]. Understanding the factors that influence fear extinction in females across different stages of their reproductive lifespan may aid in optimising exposure therapy outcomes in women
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