Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats

Knight, Parker; Chellian, Ranjithkumar; Wilson, Ryann; Behnood‐Rod, Azin; Panunzio, Stefany; Bruijnzeel, Adrie W.

doi:10.1016/j.pbb.2021.173168

Cited by 129 publications

(99 citation statements)

References 61 publications

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“…There were no differences at baseline between mechanosensitivity (spinal reflex thresholds) and emotional-affective responses (vocalizations), but females exhibited increased baseline anxiety-like behavior (OFT) compared to males in both the untreated and sham-treated control groups (see Figures 3D and 4D). This confirms findings from the literature that males spent the same or increased time in the center of the OFT compared to females at baseline [3,98], though one study found no sex difference in OFT anxiety-like behavior in a chronic spinal nerve transection pain model [99]. FE+ and FE− phenotypes showed differences in the magnitude of emotional-effective responses not only in the neuropathic pain model, as we previously reported [42], but also in the arthritis pain model (see Figure 3B,C and Figure 4B,C).…”

Section: Discussionsupporting

confidence: 90%

Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

Presto

Junell

et al. 2021

Brain Sciences

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Inter-individual and sex differences in pain responses are recognized but their mechanisms are not well understood. This study was intended to provide the behavioral framework for analyses of pain mechanisms using fear extinction learning as a predictor of phenotypic and sex differences in sensory (mechanical withdrawal thresholds) and emotional-affective aspects (open field tests for anxiety-like behaviors and audible and ultrasonic components of vocalizations) of acute and chronic pain. In acute arthritis and chronic neuropathic pain models, greater increases in vocalizations were found in females than males and in females with poor fear extinction abilities than females with strong fear extinction, particularly in the neuropathic pain model. Female rats showed higher anxiety-like behavior than males under baseline conditions but no inter-individual or sex differences were seen in the pain models. No inter-individual and sex differences in mechanosensitivity were observed. The data suggest that vocalizations are uniquely suited to detect inter-individual and sex differences in pain models, particularly in chronic neuropathic pain, whereas no such differences were found for mechanosensitivity, and baseline differences in anxiety-like behaviors disappeared in the pain models.

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Section: Discussionsupporting

confidence: 90%

Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

Presto

Junell

et al. 2021

Brain Sciences

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“…When the open field test is incorporated into a battery of tests designed to assess fear and anxiety, conflicting findings have been reported regarding sex differences and estrous cycle-linked effects on anxiety-like behavior in the same animals exposed to the EPM and to the large open field ( 59 , 61 , 97 , 102 , 109 – 113 ). Importantly, an estrous cycle-related influence on behavior in the open field does not necessarily predict the behavior of the same animal in the EPM ( 58 , 60 , 61 , 68 , 114 ).…”

Section: Animal Models Of Anxiety—behavior Of Females In Male Modelsmentioning

confidence: 98%

“…Another factor that appears to influence responding is the size of the field. Female rats in a large open field (129 × 120 × 60 cm, dim red light 18lux) spent more time in the central zone and made more central zone entries than males ( 60 ). However, using smaller arenas [70 × 70 × 70 cm arena, light level not specified ( 58 ) and 54.5 × 80 × 33 cm arena, dim red light 18lux] ( 61 ) no sex difference was observed in either distance traveled or entries into the central zone.…”

Section: Animal Models Of Anxiety—behavior Of Females In Male Modelsmentioning

confidence: 99%

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

2021

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Anxiety disorders are more prevalent in women than in men. In women the menstrual cycle introduces another variable; indeed, some conditions e.g., premenstrual syndrome, are menstrual cycle specific. Animal models of fear and anxiety, which form the basis for research into drug treatments, have been developed almost exclusively, using males. There remains a paucity of work using females and the available literature presents a confusing picture. One confound is the estrous cycle in females, which some authors consider, but many do not. Importantly, there are no accepted standardized criteria for defining cycle phase, which is important given the rapidly changing hormonal profile during the 4-day cycle of rodents. Moreover, since many behavioral tests that involve a learning component or that consider extinction of a previously acquired association require several days to complete; the outcome may depend on the phase of the cycle on the days of training as well as on test days. In this article we consider responsiveness of females compared to males in a number of commonly used behavioral tests of anxiety and fear that were developed in male rodents. We conclude that females perform in a qualitatively similar manner to males in most tests although there may be sex and strain differences in sensitivity. Tests based on unconditioned threatening stimuli are significantly influenced by estrous cycle phase with animals displaying increased responsiveness in the late diestrus phase of the cycle (similar to the premenstrual phase in women). Tests that utilize conditioned fear paradigms, which involve a learning component appear to be less impacted by the estrous cycle although sex and cycle-related differences in responding can still be detected. Ethologically-relevant tests appear to have more translational value in females. However, even when sex differences in behavior are not detected, the same outward behavioral response may be mediated by different brain mechanisms. In order to progress basic research in the field of female psychiatry and psychopharmacology, there is a pressing need to validate and standardize experimental protocols for using female animal models of anxiety-related states.

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“…Animals were weighed two times a week. On the 22 nd day of the experiment animals were tested in the Open Field test [9].…”

Section: Design Of In Vivo Experimentsmentioning

confidence: 99%

A food ingredient containing phytoecdysteroids and polyphenols from quinoa grain: technology and physiological and biochemical evaluation in vivo

et al. 2021

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An effective technological approach to produce adaptogenic microingredients is to concentrate plant biologically active substances via sorption on various matrices. The aim was to develop and evaluate in vivo the phytoecdysteroids and flavonoids concentrate extracted from quinoa grain and sorbed on the coagulated chicken egg protein. The consecutive extraction of phytoecdysteroids and flavonoids was conducted followed by sorption on the protein. The in vivo experiment was performed during 37 days using Wistar male rats. The developed concentrate was added into the diet of experimental animals in the dose 0.59±0.02 g/100 g of diet. As a stress model we used daily 40-min immobilization and exhaustive 3-hour immobilization at the end of the experiment. Urinary catecholamines content was determined, blood corticosterone, malon dialdehyde, glutathione reductase and superoxide dismutase content was determined. Phytoecdysteroids and flavonoids were concentrated 20 and 80 times respectively compared to the initial raw materials. The concentrate consumption neutralized negative effect of immobilization stress on anxiety level of Wistar rats. The significant decrease in urinary excretion of adrenaline and noradrenaline shows the pronounced adaptogenic effect of the concentrate, whereas phytoecdysteroids and flavonoids act as prostressors activating body antioxidant protection system, what is substantiated by significantly increased blood superoxide dismutase level of experimental animals.

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Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats

Cited by 129 publications

References 61 publications

Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

A food ingredient containing phytoecdysteroids and polyphenols from quinoa grain: technology and physiological and biochemical evaluation in vivo

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