Sex-specific Stress and Behavioural Responses to Human Experimenters in Rats

Abstract

The sex of the experimenter may cause stress in animal models and be a major confounding factor in preclinical research. We studied the effects of the sex of the experimenter on female and male rat anxiety behaviours using thigmotaxis in the open field test, anxiety-induced changes in brain and back temperature using infra-red thermography, and alterations in plasma concentrations of stress hormones, corticosterone and oxytocin. Female rats displayed consistently exacerbated anxiety-related behaviours along with increased infrared cutaneous temperature during repeated exposure to male experimenters. Experimental stress further intensified thermal responses to a male experimenter, especially in female rats. These behavioural responses to a male experimenter in females were associated with higher circulating corticosterone and lower oxytocin levels. Similar responses were induced by a T-shirt worn by a human male. These findings suggest that emotional and physiological responses of female rats to a male experimenter are influenced by visual and olfactory cues. These results emphasize the need to standardize and report experimenter sex throughout a study to avoid ambiguity in interpretation of the results.

Thermoregulatory dynamics reveal sex-specific inflammatory responses to experimental autoimmune encephalomyelitis in mice: Implications for multiple sclerosis-induced fatigue in females

“…Potential discrepancies between the present results and earlier investigations that have found no sex differences in the EAE mouse model might derive from age, the EAE induction regimen, the severity of the disease course, as well as procedural stress induced by animal handling, testing or the experimenter's sex. Indeed, the opposite-gender dynamics that have been recently reviewed in humans ( Chapman et al, 2018 ) may be reproduced in preclinical studies ( Faraji et al, 2021 ; Sorge et al, 2014 ) and are typically linked to psychophysiological distress. Accordingly, stress-induced hyperthermia and infection-induced fever are two distinct physiological processes that need to be differentiated by comprehensive biobehavioral testing ( Harden et al, 2015 ; Spencer et al, 2005 ; Vinkers et al, 2009 ).…”

“…The purpose of this study was to compare female and male C57BL/6 mice for susceptibility to EAE and their clinical progression using infrared (IR) thermography. IR thermography provides a non-invasive assessment of surface thermal changes in response to inflammation ( Całkosiński et al, 2015 ) and stress ( Faraji et al, 2021 ; Faraji and Metz, 2020 ; Tattersall, 2016 ) and accurately reflects variations in core temperature ( Mei et al, 2018 ). Although the average core temperature of mice under standard housing conditions is approximately between 36.5 °C and 37.5 °C, the surface temperature in mice is normally lower than the core temperature (32–36 °C) depending on the measuring tool and procedure ( Gordon, 2017 ; Mei et al, 2018 ).…”

Thermoregulatory Dynamics Reveal Sex-Specific Inflammatory Responses to Experimental Autoimmune Encephalomyelitis in Mice: Implications for Multiple Sclerosis-Induced Fatigue in Females

“…Confounding effects of the experimenter’s sex may play a critical role in causing sex-biased differences in rodent models. Indeed, the opposite-gender dynamics that have been recently reviewed in humans (Chapman, Benedict, & Schiöth, 2018) may be reproduced in preclinical studies (Faraji et al, 2021; Sorge et al, 2014) and are typically linked to psychophysiological distress. Accordingly, stress-induced hyperthermia and infection-induced fever are two distinct physiological processes that need to be differentiated by comprehensive biobehavioural testing (Harden, Kent, Pittman, & Roth, 2015; Spencer, Heida, & Pittman, 2005; Vinkers et al, 2009).…”

“…The purpose of this study was to compare female and male C57BL/6 mice for susceptibility to EAE and their clinical progression using infrared (IR) thermography. IR thermography provides a non-invasive assessment of surface thermal changes in response to inflammation (Całkosiński et al, 2015) and stress (Faraji et al, 2021; Faraji & Metz, 2020; Tattersall, 2016) and accurately reflects variations in core temperature (Mei et al, 2018). Indeed, the peripheral autonomic nervous system that regulates perspiration and surface blood perfusion, determines heat patterns and gradients during aversive experiences and physiological challenges (Ioannou, Gallese, & Merla, 2014; Redaelli et al, 2019; Vinkers et al, 2013).…”

7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice

“…Behavioural training and testing were performed during the light phase at the same time each day. Male experimenters have been shown to produce increased stress responses in rodents (Sorge et al, 2014;Faraji et al, 2022). Therefore, all experiments were undertaken by the same female experimenter.…”