Sex Differences in Hormonal Modulation of Anxiety Measured with Light-Enhanced Startle: Possible Role for Arginine Vasopressin in the Male

Toufexis, Donna; Davis, Carrie; Hammond, Alexis S.; Davis, Michael

doi:10.1523/jneurosci.0127-05.2005

Cited by 45 publications

(40 citation statements)

References 55 publications

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“…These findings suggest that the presence of testosterone may modulate operant responding. Others have observed a modulatory effect of testosterone on passive avoidance (van Oyen et al, 1980) as well as indices of 'emotional' behavior (Toufexis et al, 2005(Toufexis et al, , 2006, although there are reports for no effect on active avoidance (Beatty and Beatty, 1970;Scouten et al, 1975). Nevertheless, the present findings dissociate the role of testosterone in learned helplessness behavior that appears as a consequence of exposure to repeated uncontrollable stress, from its role in escape/avoidance behavior.…”

Section: Sex Differences In Helplessnesscontrasting

confidence: 58%

Females do not Express Learned Helplessness like Males do

Dalla

Edgecomb

Whetstone

et al. 2007

Neuropsychopharmacol

151

101

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Women are more likely than men to suffer from stress-related mental disorders, such as depression. In the present experiments, we identified sex differences in one of the most common animal models of depression, that of learned helplessness. Male and female rats were trained to escape a mild footshock each day for 7 days (controllable stress). Each rat was yoked to another rat that could not escape (uncontrollable stress), but was exposed to the same amount of shock. One day later, all stressed rats and unstressed controls were tested on a more difficult escape task in a different context. Most males exposed to uncontrollable stress did not learn to escape and were therefore helpless. In contrast, most females did learn to escape on the more difficult escape task, irrespective of whether they had been exposed to controllable or uncontrollable stress. The sex differences in helplessness behavior were not dependent on the presence of sex hormones in adulthood, because neither ovariectomy of females nor castration of males abolished them. The absence of helplessness in females was neither dependent on organizational effects of testosterone during the day of birth, because masculinized females did not express helplessness as adults. Thus, sex differences in helplessness behavior are independent of gonadal hormones in adulthood and testosterone exposure during perinatal development. Learned helplessness may not constitute a valid model for depressive behavior in women, at least as reflected by the response of female rats to operant conditioning procedures after stressful experience.

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Section: Sex Differences In Helplessnesscontrasting

confidence: 58%

Females do not Express Learned Helplessness like Males do

Dalla

Edgecomb

Whetstone

et al. 2007

Neuropsychopharmacol

151

101

View full text Add to dashboard Cite

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“…There are very few studies directly comparing males and females on fear-potentiated startle, and those that exist are conflicting with respect to differences in the acquisition and expression of fear-potentiated startle (de Jongh et al 2005;Toufexis et al 2005). We did not observe a consistent difference between sexes in fearpotentiated startle levels prior to extinction, however females showed significantly higher levels of fear after extinction.…”

Section: Discussionmentioning

confidence: 99%

Response-specific sex difference in the retention of fear extinction

Voulo

Parsons

2017

Learn. Mem.

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Fear conditioning studies in rodents allow us to assess vulnerability factors which might underlie fear-based psychopathology such as post-traumatic stress disorder (PTSD). Despite PTSD being more prevalent in females than males, very few fear conditioning studies in rodents have tested females. Our study assessed fear conditioning and extinction in male and female rats using both fear-potentiated startle and freezing behavior as measures. Rats were trained to fear cues that predicted the occurrence of shock and then subsequently exposed to an extinction training procedure where the cue was presented repeatedly in the absence of shock. Retention of the extinction memory was assessed the next day. Our results showed that females exhibited less retention of fear extinction, but only when measured by fear-potentiated startle. Our results highlight the importance of using multiple indices of fear behavior, particularly when comparing sexes on measures of extinction learning.Not all individuals who experience trauma during their lifetime will develop post-traumatic stress disorder (PTSD). One of the greatest risk factors for developing this disorder is being female, with the lifetime prevalence rate twice as high for women as it is for men (Kessler et al. 1995;Kilpatrick et al. 2013). Fear conditioning studies in rodents allow us to study the behavioral and neural mechanisms that may underlie PTSD (Parsons and Ressler 2013), yet very few fear conditioning studies in rodents have used females as subjects (Lebron-Milad and Milad 2012). Despite the increased prevalence of PTSD and other fear and anxiety-based disorders in females, nonhuman animal studies testing for sex differences in fear conditioning have largely failed to capture this difference.Fear conditioning studies typically use a procedure in which a discrete cue (e.g., auditory stimulus) signals the occurrence of an aversive stimulus, usually a brief shock. Under normal circumstances, animals learn to fear the discrete cue associated with shock and will also learn to fear the context (i.e., place) in which shock occurs. A handful of studies have directly compared animals of both sexes on tests of cued and contextual fear conditioning. Some of these reports have shown that while males and females exhibit equivalent levels of fear conditioning to discrete cues (Maren et al. 1994;Baran et al. 2009;Milad et al. 2009a;Barker and Galea 2010;Gruene et al. 2015a;Fenton et al. 2016), males often show evidence of better contextual conditioning (Maren et al. 1994;Chang et al. 2009;Barker and Galea 2010). Other studies have tested for sex differences in fear extinction learning, a form of learning through which animals learn to inhibit responding to cues that once signaled an aversive event. Over the last several years, the study of fear extinction has received considerable attention (Milad and Quirk 2012) due in part to the fact that humans with PTSD display impaired extinction (Milad et al. 2009b;Norrholm et al. 2011). Recent findings in rodents are mixed with regard t...

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“…This study (Zhang et al, 2002) showed that female rats have greater ER␤ in the lateral and medial nuclei of the amygdala and less in the BNST than males. The BNST has been shown to be critically involved in anxiety behaviors (Davis and Shi, 1999), and many studies indicate that sex differences in anxiety are mediated at the level of this limbic structure (Francis et al, 2002;Bangasser et al, 2005;Toufexis et al, 2005;Shors, 2006). Thus, males may be less sensitive than females to the disruptive effects of E on the inhibition of fear because they have more ER␤ in the BNST or other structures that mediate anxiety and/or are involved in the inhibition of fear.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Disrupts the Inhibition of Fear in Female Rats, Possibly through the Antagonistic Effects of Estrogen Receptor α (ERα) and ERβ

Toufexis¹,

Myers²,

Bowser³

et al. 2007

J. Neurosci.

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The ambiguous role of estrogen in emotional learning may result from opposing actions of estrogen receptor ␣ (ER␣) and ER␤. Using a fear-conditioning paradigm called the AXϩ, BXϪ discrimination, in which cue A comes to elicit fear and cue B becomes a safety signal, we examined the effect of 17␤-estradiol (E) and selective ER␣ and ER␤ agonists on excitatory and inhibitory fear learning. Gonadectomized (GDX) male and female rats implanted with E or selective ER␣ or ER␤ agonists were trained on the AXϩ, BXϪ discrimination and tested periodically to A, B, and AB. GDX sham-implanted male and female rats and GDX E-implanted males, but not GDX E-implanted females, exhibited less fear to AB than to A, suggesting that estrogen interferes with generalization of safety signals in female rats. ER␣ and ER␤ agonists disrupted discrimination learning in both sexes. ER␣-implanted groups had higher fear responses to all cues than did ER␤-implanted groups, suggesting that these two receptors have opposing effects in aversive discrimination learning. In contrast, neither E nor ER␣ and ER␤ agonists affected single-cue fear conditioning in either sex. These data suggest that E does not enhance fear in emotional learning but acts to disrupt the inhibition of fear in females only.

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Sex Differences in Hormonal Modulation of Anxiety Measured with Light-Enhanced Startle: Possible Role for Arginine Vasopressin in the Male

Cited by 45 publications

References 55 publications

Females do not Express Learned Helplessness like Males do

Females do not Express Learned Helplessness like Males do

Response-specific sex difference in the retention of fear extinction

Estrogen Disrupts the Inhibition of Fear in Female Rats, Possibly through the Antagonistic Effects of Estrogen Receptor α (ERα) and ERβ

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