Aversive Stimuli Alter Ventral Tegmental Area Dopamine Neuron Activity via a Common Action in the Ventral Hippocampus

Stress is a physiological, adaptive response to changes in the environment, but can also lead to pathological alterations, such as relapse in psychiatric disorders and drug abuse. Evidence demonstrates that the dopamine system plays a role in stress; however, the nature of the effects of sustained stressors on dopamine neuron physiology has not been adequately addressed. By employing a combined electrophysiological, immunohistochemical and behavioral approach, we examined the response of ventral tegmental area (VTA) dopamine neurons in rats to acute as well as repeated stressful events using noxious (footshock) and psychological (restraint) stress. We found that aversive stimuli induced a pronounced activation of the dopamine system both electrophysiologically (population activity; i.e., number of dopamine neurons firing spontaneously) and behaviorally (response to psychostimulants). Moreover, infusion of TTX into the ventral hippocampus (vHPC) reversed both behavioral and electrophysiological effects of stress, indicating that the hyperdopaminergic condition associated with stress is driven by hyperactivity within the vHPC. Therefore, the stress-induced activation of the dopamine system may underlie the propensity of stress to exacerbate psychotic disorders or predispose an individual to drug-seeking behavior. Furthermore, the vHPC represents a critical link between context-dependent DA sensitization, stress-induced potentiation of amphetamine responsivity, and the increase in DA associated with stressors.