| Women are nearly twice as likely as men to suffer from depression, which may be the result of a greater vulnerability to stress in females (Tolin & Foa, 2006). A profound sex difference in the response to stress is also observed in laboratory animals. Acute stress exposure disrupts associative learning in female rats but enhances learning in male rats (Wood & Shors, 1998). These sex differences in response to stress are mediated by different brain regions. For example, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not to modify learning in males (Maeng et al., 2010). The medial prefrontal cortex can be divided into different subregions: the prelimbic (PL) and the infralimbic (IL). There are structural and functional differences between the two areas. For instance, the prelimbic cortex projects more heavily to limbic structures such as the basolateral amygdala; in contrast, the infralimbic cortex projects more to sites involved in visceromotor processes (Vertes, 2004). Because the stress effect on learning in females relies on communication between the mPFC and the basolateral amygdala (Maeng et al., 2010), it was hypothesized that neural activity within the PL during the stressor would be necessary in order to suppress learning, whereas neural activity within the IL would not be necessary. To test this hypothesis, two separate experiments were conducted. In the first experiment, the prelimbic subregion of the mPFC in adult female rats was bilaterally inactivated with GABAA agonist muscimol. In the second experiment, the infralimbic area of the medial prefrontal cortex was bilaterally inactivated with muscimol. The animals were then exposed to acute inescapable swim stress or left unstressed. One day later, all subjects were trained with classical conditioning of the eyelid response, using a white noise conditioned stimulus paired with an eyelid stimulation unconditioned stimulus. They were trained with 100 paired trials a day for four consecutive days. Interestingly, females without neuronal activity in the PL during the stressor were able to learn well. The percentage of learned responses was significantly different from that expressed by females in which IL activity was suppressed; these females did not learn well after the stressor. Together, these data suggest that stress exposure critically engages the prelimbic, but not infralimbic, subregion of the mPFC to suppress learning in females. Moreover, because the suppressed learning after stress depends on communication between the mPFC and the amygdala, this communication must be via the prelimbic region. Together, these data suggest that neuronal communication between the prelimbic cortex and the amygdala mediates the enhanced vulnerability to stress in females. This circuit may be especially responsive in women who develop depression triggered by stressful life events. |
