Ventral tegmental area dopamine revisited: effects of acute and repeated stress

Abstract

Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression.

Reduced Ventral Tegmental Area–Hippocampal Connectivity in Children and Adolescents Exposed to Early Threat

“…Human neuroimaging studies indicate that the VTA responds to both anticipated gains as well as losses (15), consistent with electrophysiological data in nonhuman primates (16, 17). Thus, dopamine in the mesocorticolimbic system is involved in the processing and learning of novel or motivationally salient (both aversive and appetitive) events.…”

Simultaneous Changes in Sleep, qEEG, Physiology, Behaviour and Neurochemistry in Rats Exposed to Repeated Social Defeat Stress

“…In addition, social defeat stress increased extracellular DA concentrations in mesocorticolimbic areas, which could be prevented by the CRF-R2 antagonism [54], and these were not associated with high motion levels. Extracellular 5-HT and DA levels returned to baseline level after the stress procedure, suggesting that the enhanced monoamine neuronal activities probably reflect an increased orientation of attention to the provocative stimuli or attempts by the intruder to cope with the stress situation [55], while modulatory mechanisms operated after the stress stimuli. Therefore, the transient stimulation of the monoamine systems such as 5-HT and/or DA might be indicative of a large dynamic range in the adaptive plasticity of the brain, which might affect the permeability of the blood-brain barrier and consequently could result in the flattening of EEG activity as was described in long-term immobilization of stressed rats [56].…”

Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

“…By contrast, prolonged stressors such as repeated footshock 43 or restraint stress 46 increase DA neuron population activity across the medial-lateral extent of the VTA 43, 46 and DA levels in the prefrontal cortex and nucleus accumbens 47–49 . Because there are more DA neurons firing, the behaviorally salient phasic response is augmented; this is observed as an increase in amphetamine-induced locomotion 46 .…”