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Joseph LeDoux (b. 1949)
Published in Andrew P. Wickens, Key Thinkers in Neuroscience, 2018
Despite this, cortical analysis still has an important role to play in assessing dangerous situations. For example, there may be instances when we need to voluntarily confront a fearful event rather than running away. Higher thought processes will also enable us to form a more accurate understanding of the danger and make decisions based on previous experience or reasoning. Such interpretation is most likely to involve the frontal lobes and presumably it bypasses the amygdala. Another important area of the brain involved in fear is the hippocampus. Although animals with hippocampus lesions still learn a conditioned emotional response, they do not show the normal signs of fear and anxiety when placed back into the environment where the aversive events had previously taken place. In other words, hippocampal lesioned animals do not recognise whether an environment is dangerous or not.
Psychotherapy
Published in Kathleen A. Kendall-Tackett, Depression in New Mothers, 2016
Exposure therapy is specifically designed to alleviate the conditioned emotional response of the traumatic event to traumatic stimuli. After a traumatic event, patients naturally tend to avoid any memories of it, or any stimuli that reminds them of their trauma. When patients avoid processing their trauma, however, it inhibits their recovery. Exposure therapy helps patients master their fears, and counters the belief that they are weak or incompetent (National Center for PTSD, 2014b).
Targeting metabotropic glutamate receptors for rapid-acting antidepressant drug discovery
Published in Expert Opinion on Drug Discovery, 2021
mGlu5 NAMs, including MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine), its close structural analog MPEP (2-methyl-6-(phenylethynyl)pyridine), basimglurant and AZD2066, have been studied using several preclinical-validated models used in antidepressant drug research, including behavioral despair tests (forced-swim and tail suspension tests in mice), olfactory bulbectomy, acute stress models (stress-induced hyperthermia, elevated plus maze, Vogel test, conditioned emotional response, novelty-suppressed feeding, fear-potentiated startle in mice) and chronic stress models (chronic social defeat in mice and chronic mild stress in mice and rats) (reviewed in [45,46]). The high majority of studies found that the behavioral efficacy of mGlu5 NAMs was comparable to that of monoaminergic antidepressants, including SSRIs. However, the antidepressant effect was not comparable to that of ketamine, and unfortunately mGlu5 NAMs which entered in Phase II clinical trials for depression (basimglurant and AZD2066) failed to obtain convincing antidepressant efficacy [46,48]. It is however important to notice that both clinical studies retained relevant limitations. Indeed, the trial with basimglurant did not include an active comparator and, more importantly, in neither of the two studies receptor occupancy levels were above 50% at the doses used. Thus, it is yet to be established whether higher receptor occupancy levels are necessary to observe clinical efficacy.