Sex differences in the behavioural and hypothalamic–pituitary–adrenal response to contextual fear conditioning in rats

Abstract

SummaryIn recent years, special attention is being paid to sex differences in susceptibility to disease. In this regard, there is evidence that male rats present higher levels of both cued and contextual fear conditioning than females. However, little is known about the concomitant hypothalamicpituitary-adrenal (HPA) axis response to those situations which is critical in emotional memories.Here, we studied the behavioural and HPA responses of male and female Wistar rats to context fear conditioning using electric footshock as the aversive stimulus. Fear-conditioned rats showed a much greater ACTH and corticosterone response than those merely exposed to the fear conditioning chamber without receiving shocks. Moreover, males presented higher levels of freezing whereas HPA axis response was greater in females. Accordingly, during the fear extinction tests, female rats consistently showed less freezing and higher extinction rate, but greater HPA activation than males. Exposure to an open-field resulted in lower activity/exploration in fear-conditioned males, but not females, suggesting greater conditioned cognitive generalization in males than females. It can be concluded that important sex differences in fear conditioning are observed in both freezing and HPA activation, but the two set of variables are affected in the opposite direction: enhanced behavioural impact in males, but enhanced HPA responsiveness in females. Thus, the role of sex differences on fear-related stimuli may depend on the variables chosen to evaluate it, the greater responsiveness of the HPA axis in females perhaps being an important factor to be further explored.

Acute exercise enhances the consolidation of fear extinction memory and reduces conditioned fear relapse in a sex-dependent manner

“…It is well established that fear extinction learning and memory is dependent on the phase of the estrus/menstrual cycle in which female rats and humans initially learn extinction (Milad et al 2009;Daviu et al 2014). Consistent with these prior data, we observed that female rats that initially learned fear extinction in proestrus and estrus, phases of the estrus cycle during which levels of estradiol are highest, were protected against fear renewal (Fig.…”

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

“…Moreover, male rats trained to avoid an aversive arm (bright light and loud noise) in a plus maze, made more entries into the arm when the aversive stimuli were no longer present during extinction, while female rats decreased aversive arm exploration, indicating failure to extinguish the behavior (Ribeiro et al, 2010). In a separate study, males performed better in a contextual fear conditioning task, while females expressed less fear and a higher extinction rate than males (Daviu et al, 2014). Baran and colleagues (2009), however, reported that although males and females acquired fear similarly, the female rats did not extinguish as well as males.…”

“…Some studies report that females do not perform as well as males in fear conditioning and extinction learning (Baker-Andresen, Flavell, Li, & Bredy, 2013; Baran et al, 2009, 2010; Fenton et al, 2014). Male rats exhibit more freezing to the conditioned stimulus in fewer trials during fear conditioning compared to females (Aguilar et al, 2003; Baran et al, 2009, 2010; Daviu, Andero, Armario, & Nadal, 2014; Maren, De Oca, & Fanselow, 1994; Pryce, Lehmann, & Feldon, 1999; Ribeiro et al, 2010). Moreover, male rats trained to avoid an aversive arm (bright light and loud noise) in a plus maze, made more entries into the arm when the aversive stimuli were no longer present during extinction, while female rats decreased aversive arm exploration, indicating failure to extinguish the behavior (Ribeiro et al, 2010).…”

Reduced Consolidation, Reinstatement, and Renewal of Conditioned Fear Memory by Repetitive Treatment of Radix Polygalae in Mice

“…This may indicate that cues related to fear memories are not affected by RP, or that a higher dose of RP is required to be meaningful. Other types of fear-related behaviors, such as rattling, were more frequently observed during the presentation of auditory cues, which may have confounded the results by reducing the freezing time (22). …”