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Abstract
Post-traumatic stress disorder (PTSD) is a mental illness developed by vulnerable individuals exposed to life-threatening events. The pharmacological unresponsiveness displayed by the vast majority of PTSD patients has raised considerable interest in understanding the poorly known pathophysiological mechanisms underlying this disorder. Most studies in the field focused, so far, on noradrenergic mechanisms, because of their well-established role in either tuning arousal or in encoding emotional memories. However, less attention has been paid to other neural systems. Manipulations of the dopaminergic system alter behavioral responses to stressful situations and recent findings suggest that dopaminergic dysfunction might play an overriding role in the pathophysiology of PTSD. In the present review, dopaminergic mechanisms relevant for the pathogenesis of PTSD, as well as potential dopaminergic-based pharmacotherapies are discussed in the context of addressing the unmet medical need for new and effective drugs for treatment of PTSD.
Highlights
Post-traumatic stress disorder (PTSD) is the most prevalent neuropsychiatric disorder developed by vulnerable individuals exposed to life-threatening events (Benjet et al, 2016)
A dysfunction of the DAergic ventral periaqueductal gray (vPAG)/dorsal raphe nucleus (DRN) – central nucleus of the amygdala (CeA) circuitry together with a DA-dependent failure of the top-down inhibitory control exerted by the medial prefrontal cortex (mPFC) primarily over the hyperactive CeA might be responsible for the aberrant fear memory formation in PTSD patients
The human and animal data discussed in this review suggest that DAergic dysfunction is implicated in the pathophysiology of PTSD and, as a consequence, drugs targeting the central DAergic system could have a therapeutic value for the management of this disorder
Summary
Post-traumatic stress disorder (PTSD) is the most prevalent neuropsychiatric disorder developed by vulnerable individuals exposed to life-threatening events (Benjet et al, 2016). Besides these classic DAergic nuclei, relatively less-studied DAergic neurons in the ventral periaqueductal gray (vPAG) and dorsal raphe nucleus (DRN) finely modulate specific physiological functions, such as associative learning of fear, arousal states and social behavior (Matthews et al, 2016; Cho et al, 2017; Groessl et al, 2018), which are altered in several neuropsychiatric disorders including PTSD.
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