Involvement of the Ventral Tegmental Area in a Rodent Model of Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is an anxiety disorder of considerable prevalence in individuals who have experienced a traumatic event. Studies of the neural substrate of this disorder have focused on the role of areas such as the hippocampus, the amygdala and the medial prefrontal cortex. We show that the ventral tegmental area (VTA), which directly modulates these areas, is part of this circuitry. Using a rat model of PTSD, we show that a brief but intense foot shock followed by three brief reminders can cause long-term behavioral changes as shown by anxiety-like, nociception, and touch-sensitivity tests. We show that an intraperitoneal injection of a dopamine (DA) antagonist or a bilateral inactivation of the VTA administered immediately before the traumatic event decrease the occurrence or intensity of these behavioral changes. Furthermore, we show that there is a significant decrease of baseline VTA dopaminergic but not GABAergic cell firing rates 2 weeks after trauma. Our data suggest that VTA DA neurons undergo long-term physiological changes after trauma and that this brain area is a crucial part of the circuits involved in PTSD symptomatology. Neuropsychopharmacology (2013) 38, 350-363; doi:10.1038/npp.2012.189; published online 26 September 2012