However, BNZ is associated with enhancing access to emotional memories (but not to procedural memory). Actually, until the 1970s, one of the major techniques to treat PTSD was via the “benzodiazepine interview,” which used BNZ (or sodium pentothal) in order to help the individual to go through full re-experience of the event. However,

how does this fit with our line of reasoning that reducing fear memory is beneficial? In a small study, Gelpin et al22 compared at 1-and 6-month follow-up individuals who received Inhibitors,research,lifescience,medical BNZ (clonazepam 2.6 mg/day or alprazolam 2.5 mg/day) with those who did not receive it. Out of the 13 who received BNZ, 9 developed PTSD, as compared with 3 of the 13 controls. These findings were also replicated by Mellman Inhibitors,research,lifescience,medical et al in a small study.23 In a unique animal model, which is based on setting affected (rats) apart from the unaffected,24 administration of alprazolam 1 hour after the exposure was associated with significantly more extreme behavioral response (the behavioral equivalent of PTSD) for the rats who were given alprazolam as compared with those

who got saline.25 Hence, some pilot human data, plus a signal from animal studies suggest that early administration of BNZ might interfere with the Selleckchem MLN8237 normal potent spontaneous recovery. Hypothalamic-pituitary-adrenal axis, PTSD, and BNZ Glucocorticoids were found to reduce Inhibitors,research,lifescience,medical phobic fear in humans.26 Individuals with arachnophobia who were injected with Cortisol 1 hour before exposure reported less fear (as measured on a visual analog scale) as Inhibitors,research,lifescience,medical compared with individuals who got saline. Stress is associated with activation of the hypothalamicpituitary-adrenal (HPA) axis, and consequently with secretion of hydrocortisone. What is the effect of BNZ on this normal, primary cornerstone of the normal response to stress? What is the effect of BNZ on Cortisol? Why does administration of BNZ seem to interfere with the normal recovery process? Administration of BNZ abolishes the expected activation (the normal response) of the HPA axis. Inhibitors,research,lifescience,medical The HPA axis is the main component in the

neuroendocrine response to acute and chronic stress (Figure 4). In response to stress, a chain of reactions Linifanib (ABT-869) stimulates the adrenal cortex to synthesize and release glucocorticoids, in particular Cortisol. These hormones are instrumental in adaptation to stress.27 A main function appears to be in the regulation and containment of the sympathetic and parasympathetic responses to stress (ie, changes in heart rate, blood pressure, respiration), responses that help the body accommodate to an immediate demand. In animal studies, it has been demonstrated that blunted HPA-axis response increased PTSD-like reactions in rats exposed to trauma,28 which strengthens the notion that an intervention aimed at bolstering this natural response with an early intervention immediately after the trauma could help reduce PTSD (Figure 5). Figure 4. The hypothaiamic-pituitary-adrenal axis. Figure 5.