Stress facilitates classical conditioning in males, but impairs classical conditioning in females through activational effects of ovarian hormones

Abstract

Exposure to restraint and brief intermittent tailshocks facilitates associative learning of the classical conditioned eyeblink response in male rats. Based on evidence of sex differences in learning and responses to stressful events, we investigated sexually dimorphic effects of a stressor of restraint and intermittent tailshock on classical eyeblink conditioning 24 h after stressor cessation. Our results indicate that exposure to the acute stressor had diametrically opposed effects on the rate of acquisition of the conditioned response in male vs. female rats. Exposure to the stressor facilitated acquisition of the conditioned response in males, whereas exposure to the same stressful event dramatically impaired acquisition in females. We further demonstrate that the stress-induced impairment in female conditioning is dependent on the presence of ovarian hormones. Conditioning of stressed sham-ovariectomized females was significantly impaired relative to the unstressed controls, whereas conditioning in stressed ovariectomized females was not impaired. We present additional evidence that estrogen mediates the stressinduced impairment in female acquisition. Females administered sesame oil vehicle and then stressed were significantly impaired relative to their unstressed controls, whereas females administered the estrogen antagonist tamoxifen prior to stress were not impaired. In summary, these results indicate that exposure to the same aversive event can induce opposite behavioral responses in males vs. females. These effects underscore sex differences in associative learning and emotional responding, and implicate estrogen in the underlying neuronal mechanism.

Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

“…Interestingly, these sex differences on the impact of stress also expand to other forms of learning, although the effects are reversed for cued and spatial learning. Similar to our results, acute stress exposure impairs classical eye-blink conditioning in female rats while enhancing performance in males (Wood & Shors, 1998). On the other hand, stress impairs performance in the Y maze and radial arm maze in males but not in females (Bowman, Beck, & Luine, 2003;Conrad, Grote, Hobbs, & Ferayorni, 2003).…”

Estrogen-mediated effects on depression and memory formation in females

“…Although unresponsive to acquiring new associations, it is not the case that the female could not respond (Wood and Shors, 1998). Neither stress nor gender altered the number of spontaneous blinks or blinks in response to auditory stimuli prior to training.…”

“…1B) (Shors et al, 2000 for review;Shors, 2000Shors, , 1998Beylin and Shors, 1998;Servatius and Shors, 1994;Shors et al, 1992). In contrast, exposure to the very same stressor dramatically impaired conditioning in females (Wood and Shors, 1998;Shors et al, 1998;Wood et al, 2000) (Fig. 1A and 1B).…”

“…The effect of stress on conditioning in females is sensitive to both these factors. First of all, the effect of stress is prevented by removal of ovarian hormones via ovariectomy (Wood and Shors, 1998) (Fig. 2A).…”

Females do not Express Learned Helplessness like Males do

“…Even though females did learn to escape after exposure to uncontrollable stress, this effect may be limited to tests of operant conditioning. During training with other types of conditioning procedures, performance in females is actually quite susceptible to the negative consequences of uncontrollable stressful experience (Shors, 2006;Wood and Shors, 1998). For example, with classical eyeblink conditioning procedures, female rats express a severe deficit in learning after exposure to the same regimen of repeated uncontrollable stress as used here (Leuner et al, 2004).…”