24 Although propranolol administration in this study did not prevent the development of PTSD, it may have blocked traumatic memory consolidation,25 and therefore may reduce the severity and/or chronicity of PTSD. It is important to note, however, that this finding contradicts those from an earlier study.26 Various antiadrenergic agents have been tested for their therapeutic efficacy in the treatment of PTSD in open-label trials; there is a paucity of controlled trials.20 Serotonin Serotonin (5HT), is a monoamine neurotransmitter synthesized

from the amino acid tryptophan. Neurons containing 5HT originate in the dorsal and median raphe nuclei Inhibitors,research,lifescience,medical in the brain stem and project to multiple forebrain regions, including the amygdala, bed nucleus of the stria terminalis, hippocampus, hypothalamus, and prefrontal cortex. 5HT has

roles in regulating sleep, appetite, sexual behavior, aggression/impulsivity, motor function, analgesia, and neuroendocrine funtion. Inhibitors,research,lifescience,medical Not surprisingly, given its connectivity and broad homeostatic role, 5HT has been implicated in the modulation of affective and novel stress responses, as well as a role in PTSD. Inhibitors,research,lifescience,medical Although the mechanisms are not entirely clear, the effects of 5HT on affective and stress responses vary according to stressor intensity, brain region, and Dovitinib kinase receptor type. It is believed that 5HT neurons of the dorsal raphe mediate anxiogenic effects via 5HT2 receptors through projections to the amygdala and hippocampus. In contrast, 5HT neurons from the median raphe are thought to mediate anxiolytic effects, facilitate extinction and suppress encoding of learned associations via 5HT1A receptors. Chronic exposure to stressors induces upregulation Inhibitors,research,lifescience,medical of 5HT2 and downregulation of 5HT1A receptors in animal models. Further, 5HT1A knockouts exhibit increased stress responses. Inhibitors,research,lifescience,medical The 5HT system interacts with the CRH and NE systems in coordinating affective and stress responses.19,27 Indirect evidence suggests a role for 5HT in PTSDrelated behaviors including

impulsivity, hostility, aggression, depression, and suicidally. In addition, 5HT presumably mediates the therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs). A recent small and controversial study suggests that the street drug 3,4-Methylenedioxymetharnphetamine (also known as .MDMA or “ecstasy”), which alters Entinostat central serotonin transmission, has therapeutic potential in the treatment of PTSD.28 Other evidence for altered 5 HT neurotransmission in PTSD includes decreased serum concentrations of 5HT, decreased density of platelet 5HT uptake sites, and altered responsiveness to CNS serotonergic challenge in patients diagnosed with PTSD.19,27 However, no differences in CNS 5HT1A receptor binding were detected in patients with PTSD compared with controls using PET imaging.