Strain and sex differences in fear conditioning: 22 kHz ultrasonic vocalizations and freezing in rats.

Abstract

Strain and sex differences in fear conditioning were investigated in two commonly used laboratory rats: Sprague Dawleys and Long-Evans. Twenty-two kHz ultrasonic vocalization (USV) distress calls and freezing behavior were used to measure fear responses to contextual and auditory conditioned stimuli (CSs), which were previously paired with a footshock unconditioned stimulus (US). Both strain and sex had significant effects on USVs and freezing during training and subsequent context and tone tests. Overall, the male Sprague Dawley rats froze and emitted USVs more than the other groups. Additionally, levels of freezing and USVs were differentially influenced by the type of CS (context or tone). These results suggest that species-specific defense responses in laboratory rats are highly influenced by the strain and sex of the subject, and that these factors should be considered in future fear conditioning studies.

The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

“…In fact, vocalizations at this point were so low that the lack of significance between the two groups could be explained by a floor effect. Meanwhile, freezing remained high in both conditions, evidencing that freezing and vocalizations are differently responsive to environmental factors as previously reported (Jelen et al, 2003 ; Graham et al, 2009 ). The fact that STN lesions induce dissociation between the two behavioral responses further supports the view that they may reflect separable aspects of aversive processes.…”

Isolation‐induced ultrasonic vocalizations in pups: A comparison between Long‐Evans, Sprague–Dawley, and Wistar rats

“…Several aspects, however, argue against such a conclusion: For one, the positive relationships between pup USV and adult anxiety were observed in selectively‐bred lines of rats, but were either not found in “normal” stocks (WU, Wöhr & Schwarting, ) or were even negatively related to adult anxiety there (Schwarting & Pawlak, ). Second, it was found that adult SD rats emitted more 22‐kHz calls and froze more in a fear‐conditioning paradigm than LE rats (Graham et al, ) or that SD rats showed more 22‐kHz calls and immobility in a social intruder paradigm than WU rats (Walker et al, ). We also found more 22‐kHz USV in a fear‐conditioning paradigm in SD than WU rats (Schwarting, ), and Turner and Burns () considered adult LE rats to be more anxious than SD rats.…”

“…Second, it was found that adult SD rats emitted more 22-kHz calls and froze more in a fear-conditioning paradigm than LE rats (Graham et al, 2009) or that SD rats showed more 22-kHz calls and immobility in a social intruder paradigm than WU rats (Walker et al, 2009).…”

“…Several studies have shown that these stocks can differ at several levels, including brain (Rex, Voigt, Gustedt, Beckett, & Fink, 2004;Swerdlow et al, 2005;Zamudio, Fregoso, Miranda, Cruz, & Flores, 2005) and pharmacological reactivity (Arnold, Dielenberg, & McGregor, 2010;Entlerova et al, 2013;Koss, Einat, Schloesser, Manji, & Rubinow, 2012;Manduca et al, 2014;Qu et al, 2009;Rex et al, 2004;Swerdlow et al, 2005). Regarding behavior, stock differences were obtained in several functions, especially anxiety (Rex et al, 2004), fear-conditioning (Graham, Yoon, Lee, & Kim, 2009;Keeley, Bye, Trow, & McDonald, 2015;Walker, Naicker, Hinwood, Dunn, & Day, 2009), defensive reactions to predator odors (Rosen, West, & Donley, 2006;Staples & McGregor, 2006), stress reactivity (Faraday, 2002), openfield behavior (Zamudio et al, 2005), novelty-seeking (Walker et al, 2009), social play behavior (Ku, Weir, Silverman, Berman, & Bauman, 2016;Manduca et al, 2014), spatial learning (Keeley et al, 2015), object discrimination (Andrews, Jansen, Linders, Princen, & Broekkamp, 1995), or prepulse inhibition (Faraday, Blakeman, & Grunberg, 2005;Qu et al, 2009;Varty & Higgins, 1994). While it is difficult to extract a consistent pattern, WU rats appear more anxious than other stocks in a number of different situations, whereas SD rats appear to exhibit particularly high levels of social play behavior.…”

Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

“…While female sex remains a risk factor, the sexual dimorphism present in the acquisition (Inslicht et al, 2013), presentation (Olff et al, 2007;Hourani et al, 2015), and treatment efficacy (Blain et al, 2010) of PTSD suggests that there are underlying biological differences based on sex that need to be investigated separately in both sexes (Cahill, 2003a(Cahill, ,b, 2006Pineles et al, 2017). Similarly to humans, rodent models of PTSD-associated behaviors show sex differences in response to trauma (Faraday, 2002;Adamec et al, 2006;Graham et al, 2009;Cohen and Yehuda, 2011;Toth et al, 2016;Pineles et al, 2017;Deslauriers et al, 2019). The RISP model was developed in male rats and we hypothesize that female rats will require different behavioral parameters for classification and PTSD-phenotyping.…”