The VTA plays an important role in a number of processes, including reward cognition (motivational salience, associative learning, and positively-valenced emotions) and orgasm,[2] among others, as well as several psychiatric disorders.
Neurobiologists have often had great difficulty distinguishing the VTA in humans and other primate brains from the substantia nigra (SN) and surrounding nuclei.
[citation needed] The VTA is a heterogeneous region consisting of a variety of neurons that are characterized by different neurochemical and neurophysiological properties.
[13] The two primary efferent fiber projections of the VTA are the mesocortical and the mesolimbic pathways, which correspond to the prefrontal cortex and nucleus accumbens respectively.
[14][15] In addition, experiments in rodents have identified a mesohabenular pathway consisting of VTA neurons that do not release dopamine, but glutamate and GABA.
[14] Because they develop from common embryonic tissue and partly overlap in their projection fields, Dopaminergic cell groups lack clear anatomical boundaries.
During the development of the mammalian brain, both substantia nigra (SN) and VTA neurons initially project to the dorsolateral and ventromedial striatum.
In 2006, MRI studies by Helen Fisher and her research team found and documented various emotional states relating to intense love correlated with activity in the VTA, which may help explain obsessive behaviors of rejected partners, since this is shared by the reward system.
[21] However, V1aR expression was not related to female directed song rates, which may indicate a selective role of vasotocin in the VTA on pair maintenance versus courtship behavior.
[26] In addition, there is a sizable population of GABAergic neurons in the rostromedial tegmental nucleus (RMTg), a functionally distinct brain structure.
[9][10] These GABAergic neurons regulate the firing of their dopaminergic counterparts that send projections throughout the brain to, but not limited to, the following regions: the prefrontal cortex, the nucleus accumbens, and the locus coeruleus.
[27] The dopamine reward circuitry in the human brain involves two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.
[citation needed] The dopaminergic neurons of the substantia nigra and the ventral tegmental area of the midbrain project to the dorsolateral caudate/putamen and to the ventromedially located nucleus accumbens, respectively, establishing the mesostriatal and the mesolimbic pathways.
Current research is examining the subtle difference between the neurons that are involved in these conditions and trying to find a way to selectively treat a specific dopamine projection.
In the VTA of addicted individuals, the activity of the dopamine-synthesizing enzyme tyrosine hydroxylase increases, as does the ability of these neurons to respond to excitatory inputs.
The latter effect is secondary to increases in the activity of the transcription factor CREB and the up regulation of GluR1, an important subunit of AMPA receptors for glutamate.
These alterations in neural processing could account for the waning influence of adaptive emotional signals in the operation of decision making faculties as drug-seeking and drug-taking behaviors become habitual and compulsive.
The withdrawal phenomenon occurs because the deficit in reward functioning initiates a distress cycle wherein the drugs become necessary to restore the normal homeostatic state.
Recent research has shown that even after the final stages of withdrawal have been passed, drug-seeking behavior can be restored if exposed to the drug or drug-related stimuli.