While the acute stress response is an important and necessary mechanism to adapt

to environmental changes that occur throughout life thus promoting effective coping, severe or chronic stress can result in allostatic load and is also a contributing risk factor for the development of several psychiatric disorders such as depression and post-traumatic stress disorder (PTSD) (McEwen and Wingfield, 2003 and McEwen, 2007). However, it is also important to note that many stress-exposed individuals do not develop stress-related psychiatric see more disorders (Charney and Manji, 2004, Yehuda and LeDoux, 2007 and Caspi et al., 2003) and are thus more resilient to the negative consequences of stress than others.

Modulators resilience to stress is the ability to cope with environmental challenges, ensuring survival, while susceptibility to the negative consequences of stress seems to result from an improper functioning of the systems of resilience or an amplification of the stress experience (Karatsoreos and McEwen, 2013), which in turn can result in maladaptive physiological and behavioural responses. Such maladaptive responses to stress may increase the risk for the development of stress-related psychiatric disorders, and as such great effort is being made to elucidate the neural processes that underlie stress-resilience in the hope ABT-199 cost that these might be then exploited for drug development (Franklin Tamara et al., 2012, Russo et al., 2012, Wu et al., 2013 and Hughes, 2012). The hippocampus is a key brain area involved in the regulation of the stress response, exerting negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis (Jacobson and Sapolsky, 1991), the system within the body responsible for the release of glucocorticoid stress hormones. Stressors rapidly stimulate the secretion of corticotropin-releasing

factor and vasopressin from parvocellular neurons of the paraventricular nucleus of the hypothalamus and this stimulates the release of adrenocorticotropic hormone from the anterior pituitary, which in turn stimulates the release of 17-DMAG (Alvespimycin) HCl glucocorticoid stress hormones from the adrenal cortex into the circulation (Cullinan et al., 1995). These glucocorticoids, cortisol in humans and corticosterone in rodents (Herman and Cullinan, 1997), feedback onto two types of receptors in the brain: the mineralocorticoid receptors – MR and glucocorticoid receptors – GR, which are highly expressed in limbic structures of the brain, including the hippocampus (Morimoto et al., 1996). While hippocampal MR mediates the effects of glucocorticoids on assessment of the stressor and initiation of the stress response, GR acts in the consolidation of acquired information (de Kloet et al., 2005 and De Kloet et al., 1998).