No effect of sex and estrous cycle on the fear potentiated startle response in rats

Zhao, Yulong; Bijlsma, Elisabeth Y.; Verdouw, Monika P.; Groenink, Lucianne

doi:10.1016/j.bbr.2018.05.022

Cited by 24 publications

(21 citation statements)

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“…In tests using conditioned fear paradigms (FPS and conditioned fear to context), females as a group responded in the same way as males, and we were unable to detect any difference in responsiveness at different stages of the oestrous cycle. Our findings are in agreement with previous reports of similar experiments using Wistar and Lewis rats (Cossio et al, 2016; Maeng et al, 2015; Pryce et al, 1999; Zhao et al, 2018). On the other hand, they contrast with results of other studies using these tests in which males were reported to be more responsive than females (de Jongh et al, 2005; Gresack et al, 2009; Maren et al, 1994; Pettersson et al, 2016).…”

Section: Discussionsupporting

confidence: 94%

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats

et al. 2019

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Background and aims: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX). Methods: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour. Results: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context. In a light switch-off test where rats move from one compartment of a shuttle-box to the other to turn off an aversive light, females displayed enhanced responding in late dioestrus. During isolation restraint stress females in late dioestrus emitted three times more 22 kHz ultrasound vocalisations (USV) than at other cycle stages. Using the USV test, short-term administration of low-dose FLX (1.75 mg kg−1, i.p.) designed to blunt the sharp fall in brain allopregnanolone concentration during late dioestrus but without affecting 5-HT systems, prevented the increase in isolation stress-evoked USVs. Conclusions: The light switch-off and isolation restraint-induced USV tests evoke unconditioned adverse emotional responses that are ethologically relevant and sensitive to oestrous cycle stage. The USV test fulfils many criteria required of a model for premenstrual syndrome in women. Using the USV test, short-term administration of FLX to increase brain allopregnanolone concentration without affecting 5-HT systems prevented the increased USV responding in late dioestrus. Short-term low-dose FLX treatment may have potential to alleviate development of adverse premenstrual symptoms in women.

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Section: Discussionsupporting

confidence: 94%

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats

et al. 2019

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“…Although the literature contains many conflicting reports on estradiol’s effects on fear- and anxiety-related behavior, our finding in LAP1 females is consistent with at least one report indicating anxiolytic effects of estrogen replacement on contextual fear behavior in rats [76]. Other studies in cycling rats have not found effects of estrous cycle on the expression of FPS [77,78,79]. These findings highlight the importance of monitoring the estrous cycle and, if possible, measuring estradiol when testing both males and females in fear-conditioning studies.…”

Section: Discussionsupporting

confidence: 90%

Endocannabinoids and Fear-Related Behavior in Mice Selectively Bred for High or Low Alcohol Preference

2019

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Alcohol use disorders (AUDs) have a high incidence of co-morbidity with stress-related psychopathologies, such as post-traumatic stress disorder (PTSD). Genetic and pharmacological studies support a prominent role for the endocannabinoid system (ECS) in modulating stress-related behaviors relevant to AUDs and PTSD. Mouse lines selectively bred for high (HAP) and low (LAP) alcohol preference show reproducible differences in fear-potentiated startle (FPS), a model for PTSD-related behavior. The first experiment in this study assessed levels of the endocannabinoids, anandamide (AEA) and sn-2 arachidonylglycerol (2-AG), in the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP) of male and female HAP1 and LAP1 mice following the expression of FPS to determine whether ECS responses to conditioned-fear stress (FPS) were correlated with genetic propensity toward high or low alcohol preference. The second experiment examined effects of a cannabinoid receptor type 1 agonist (CP55940) and antagonist (rimonabant) on the expression of FPS in HAP1 and LAP1 male and female mice. The estrous cycle of females was monitored throughout the experiments to determine if the expression of FPS differed by stage of the cycle. FPS was greater in male and female HAP1 than LAP1 mice, as previously reported. In both experiments, LAP1 females in diestrus displayed greater FPS than LAP1 females in metestrus and estrus. In the AMG and HIP, AEA levels were greater in male fear-conditioned HAP1 mice than LAP1 mice. There were no line or sex differences in effects of CP55940 or rimonabant on the expression of FPS. However, surprisingly, evidence for anxiogenic effects of prior treatment with CP55940 were seen in all mice during the third drug-free FPS test. These findings suggest that genetic differences in ECS function in response to fear-conditioning stress may underlie differences in FPS expression in HAP1 and LAP1 selected lines.

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“…Sample size calculations for both experiments were based on previous studies in our laboratory (Bijlsma et al 2015). A methodological study from our lab showed that male and female rats do not differ in their fear-potentiated startle response (Zhao et al 2018a). The present study was therefore only performed in male rats to reduce the total number of animals needed.…”

Section: Methodsmentioning

confidence: 99%

Activation of somatodendritic 5-HT1A autoreceptors reduces the acquisition and expression of cued fear in the rat fear-potentiated startle test

et al. 2018

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Rationale Fear conditioning is an important factor in the etiology of anxiety disorders. Previous studies have demonstrated a role for serotonin (5-HT) 1A receptors in fear conditioning. However, the relative contribution of somatodendritic 5-HT 1A autoreceptors and post-synaptic 5-HT 1A heteroreceptors in fear conditioning is still unclear. Objective To determine the role of pre- and post-synaptic 5-HT 1A receptors in the acquisition and expression of cued and contextual conditioned fear. Methods We studied the acute effects of four 5-HT 1A receptor ligands in the fear-potentiated startle test. Male Wistar rats were injected with the 5-HT 1A receptors biased agonists F13714 (0–0.16 mg/kg, IP), which preferentially activates somatodendritic 5-HT 1A autoreceptors, or F15599 (0–0.16 mg/kg, IP), which preferentially activates cortical post-synaptic 5-HT 1A heteroreceptors, with the prototypical 5-HT 1A receptor agonist R(+)8-OH-DPAT (0–0.3 mg/kg, SC) or the 5-HT 1A receptor antagonist WAY100,635 (0–1.0 mg/kg, SC). Results F13714 (0.16 mg/kg) and R(+)-8-OH-DPAT (0.03 mg/kg) injected before training reduced cued fear acquisition. Pre-treatment with F15599 or WAY100,635 had no effect on fear learning. In the fear-potentiated startle test, F13714 (0.04–0.16 mg/kg) and R(+)-8-OH-DPAT (0.1–0.3 mg/kg) reduced the expression of cued and contextual fear, whereas F15599 had no effect. WAY100,635 (0.03–1.0 mg/kg) reduced the overall startle response. Conclusions The current findings indicate that activation of somatodendritic 5-HT 1A autoreceptors reduces cued fear learning, whereas 5-HT 1A receptors seem not involved in contextual fear learning. Moreover, activation of somatodendritic 5-HT 1A autoreceptors may reduce cued and contextual fear expression, whereas we found no evidence for the involvement of cortical 5-HT 1A heteroreceptors in the expression of conditioned fear.

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No effect of sex and estrous cycle on the fear potentiated startle response in rats

Cited by 24 publications

References 94 publications

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats

Endocannabinoids and Fear-Related Behavior in Mice Selectively Bred for High or Low Alcohol Preference

Activation of somatodendritic 5-HT1A autoreceptors reduces the acquisition and expression of cued fear in the rat fear-potentiated startle test

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