Elucidating the fear - maintaining properties of the Ventral Tegmental Area

The ventral tegmental area (VTA) and its dopaminergic (DA) mesocorticolimbic projections are thought to be essential in the brain’s reward neurocircuitry. In humans and animal experimental subjects, mild electrical VTA stimulation increases dopamine levels and can induce euphoria. Paradoxically, aversive stimuli activate VTA neurons and forebrain DA activity, and excessive electrical stimulation of the VTA exaggerates fearfulness. Research suggests that experimental manipulation of either the amygdala or the VTA has similar effects on the acquisition and expression of Pavlovian conditioned fear. Recently it was demonstrated that electrical stimulation of the amygdala produced fear extinction deficits in rats. Fear extinction involves the progressive dissipation of conditioned fear responses by repeated nonreinforced exposure to a conditioned stimulus (CS). Maladaptive states of fear in fear-related anxiety disorders, such as post-traumatic stress disorders (PTSD) or specific phobias are thought to reflect fear extinction learning deficits. The primary purpose of the present study was to examine the effects of intraVTA stimulation on fear extinction learning. Using fear-potentiated startle as a behavioural index of conditioned fear, it was found that 120 VTA stimulations paired or unpaired with non-reinforced CS presentations impaired the extinction of conditioned fear. This effect was not apparent in rats that received electrical stimulation of the substantia nigra (SN), suggesting that not all midbrain regions respond similarly. Electrical stimulation parameters did not have aversive affects because rats failed to show fear conditioning when electrical VTA stimulation was used as the unconditioned stimulus. Also, VTA stimulation did not alter conditioned fear expression in non-extinguished animals. Based on the results it is suggested that VTA activation disinhibited conditioned fear responding. Therefore, VTA neuronal excitation by aversive stimuli may play a role in fear-related anxiety disorders thought to reflect extinction learning deficits.