The somatodendritic release of dopamine in the ventral tegmental area and its regulation by afferent transmitter systems

The release of dopamine in the ventral tegmental area (VTA) plays an important role in the autoinhibition of the dopamine neurons of the mesocorticolimbic system through the activation of somatodendritic dopamine D2 autoreceptors. Accordingly, the intra-VTA application of dopamine D2 receptor agonists reduces the firing rate and release of dopamine in the VTA, and this control appears to possess a tonic nature because the corresponding antagonists enhance the somatodendritic release of the transmitter. In addition, the release of dopamine in the VTA is increased by potassium or veratridine depolarization and abolished by tetrodotoxin and calcium omission. Overall, it appears that the somatodendritic release of dopamine is consistently lower than that in nerve endings. Apart from intrinsic dopaminergic mechanisms, other transmitter systems such as serotonin, noradrenaline, acetylcholine, GABA and glutamate play a role in the control of the activity of dopaminergic neurons of the VTA, although the final action depends on the particular receptor involved as well as the neuronal type where it is localized. Given the involvement of the mesocorticolimbic dopaminergic systems in the pathogenesis of severe neuropsychiatric disorders such as schizophrenia, the knowledge of the factors that regulate the release of dopamine in the VTA could provide new insight into the ethiogenesis of the disease as well as its implication on the mechanisms of action of therapeutic drugs.