The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the
midline on the floor of the
midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal ( alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
. The VTA is the origin of the
dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate do ...
cell bodies of the
mesocorticolimbic dopamine system and other
dopamine pathways; it is widely implicated in the drug and natural
reward circuitry of the
brain
The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...
. The VTA plays an important role in a number of processes, including
reward cognition (
motivational salience,
associative learning, and
positively-valenced emotions) and
orgasm
Orgasm (from Greek , ; "excitement, swelling") or sexual climax is the sudden discharge of accumulated sexual excitement during the sexual response cycle, resulting in rhythmic, involuntary muscular contractions in the pelvic region charact ...
, among others, as well as several
psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
to the caudal
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is ...
and several regions in between.
Structure
Neurobiologists have often had great difficulty distinguishing the VTA in humans and other primate brains from the
substantia nigra (SN) and surrounding nuclei. Originally, the ventral tegmental area was designated as a ‘nucleus’, but over time ‘area’ became the more appropriate term used because of the heterogeneous
cytoarchitectonic features of the region and the lack of clear borders that separate it from adjacent regions. Because of the selective
limbic-related afferents to the VTA, the cells of the VTA are given the designation A10 to differentiate them from surrounding cells.
Location
The ventral tegmental area is in the midbrain between several other major areas, some of which are described here. The
mammillary bodies and the posterior
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...
, both included in the
diencephalon
The diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is asso ...
, extend rostrally from the VTA. The
red nucleus is situated laterally and oculomotor fibers are situated ventromedially to the VTA. The
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of ...
and the
hindbrain lie caudally to the VTA. Finally, the substantia nigra is located laterally to the VTA.
Subdivisions
In 1987, Oades identified four primary nuclei in the
VTA A10 group of cells: the nucleus paranigralis (Npn), the nucleus parabrachialis pigmentosus (Npbp), the nucleus interfascicularis (Nif), and the nucleus linearis (Nln) caudalis and rostralis. Presently, scientists divide the VTA up into four similar zones that are called the paranigral nucleus (PN), the parabrachial pigmented area (PBP), the parafasciculus retroflexus area (PFR), and the
rostromedial tegmental nucleus The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the ve ...
(RMTg), which approximately adhere to the previous divisions. Some definitions of the VTA also include the midline nuclei (i.e. the interfascicular nucleus, rostral linear nucleus, and central linear nucleus).
The PN and PBP are rich in dopaminergic cells, whereas the other two regions have low densities of these neurons. The PFR and RMTg contain a low density of
tyrosine hydroxylase (TH)-positive cell bodies that are small in size and lightly stain; the RMTg is composed mostly of GABAergic cells. On the other hand, the PN and PBP consist mainly of medium to large sized TH-positive cell bodies that stain moderately.
Inputs
Almost all areas receiving projections from the VTA project back to it. Thus, the ventral tegmental area is reciprocally connected with a wide range of structures throughout the brain suggesting that it has a role in the control of function in the
phylogenetically newer and highly developed
neocortex
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, ...
, as well as that of the phylogenetically older limbic areas.
The VTA is a heterogeneous region consisting of a variety of neurons that are characterized by different neurochemical and neurophysiological properties. Therefore, glutamatergic and GABAergic inputs are not exclusively inhibitory nor exclusively excitatory.
The VTA receives glutamatergic afferents from the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
,
pedunculopontine tegmental nucleus (PPTg),
laterodorsal tegmental nucleus,
subthalamic nucleus,
bed nucleus of the stria terminalis,
superior colliculus
In neuroanatomy, the superior colliculus () is a structure lying on the roof of the mammalian midbrain. In non-mammalian vertebrates, the homologous structure is known as the optic tectum, or optic lobe. The adjective form '' tectal'' is commo ...
,
periaqueductal gray,
lateral habenula
In neuroanatomy, habenula (diminutive of Latin ''habena'' meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the ...
,
dorsal raphe nucleus, and
lateral hypothalamic
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognit ...
and
preoptic areas.
These glutamatergic afferents play a key role in regulating VTA cell firing. When the glutamatergic neurons are activated, the firing rates of the dopamine neurons increase in the VTA and induce burst firing. Studies have shown that these glutamatergic actions in the VTA are critical to the effects of drugs of abuse. In contrast, the
tail of the ventral tegmental area The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the ve ...
(tVTA, the RMTg) projects to the VTA with GABAergic afferents, functioning as a "master brake" for the VTA dopamine pathways.
GABAergic inputs to the VTA also include the
nucleus accumbens,
ventral pallidum,
dorsal raphe nucleus,
lateral hypothalamus
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cogn ...
,
periaqueductal gray,
bed nucleus of the stria terminalis, and
rostromedial tegmental nucleus The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the ve ...
(RMTg).
The
lateral habenula
In neuroanatomy, habenula (diminutive of Latin ''habena'' meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the ...
can also exert an inhibitory effect on dopaminergic neurons in the VTA by exciting RMTg GABAergic neurons, which is thought to play an important role in reward prediction errors. Subpallidal afferents into the VTA are mainly
GABAergic
In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...
and, thus, inhibitory.
There is a substantial pathway from the subpallidal area to the VTA.
When this pathway is disinhibited, an increase in the dopamine release in the
mesolimbic pathway amplifies locomotor activity.
There are also cholinergic inputs to the VTA, although less studied than the glutamatergic and GABAergic inputs. Optogenetic studies in mice looking at cholinergic inputs from the
pedunculopontine tegmental nucleus (PPTg) and the
laterodorsal tegmental nucleus demonstrate that these circuits reinforce the discharge properties of VTA neurons, suggesting a modulatory influence on reward circuits.
Outputs
The two primary efferent fiber projections of the VTA are the
mesocortical and the
mesolimbic pathways, which correspond to the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
and
nucleus accumbens respectively.
In addition, experiments in rodents have identified a mesohabenular pathway consisting of VTA neurons that do not release
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...
, but
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
and
GABA. Other VTA projections, which utilize
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...
as their primary
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
, are listed below.
* Ventral tegmental area (VTA) projections
:* VTA →
Amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex v ...
:*VTA →
Entorhinal cortex
The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time.Integrating time from experience in ...
:* VTA →
Cingulate gyrus
:* VTA →
Hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
:* VTA →
Nucleus accumbens
:* VTA →
Olfactory bulb
The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (O ...
:* VTA →
Prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
Development
Because they develop from common embryonic tissue and partly overlap in their projection fields,
Dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate do ...
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. However, at birth the SN dopaminergic neurons project exclusively into the dorsolateral striatum, and the VTA dopaminergic neurons project solely into the ventromedial striatum. This pruning of connections occurs through the elimination of the unnecessary collaterals.
Function
As stated above, the VTA, in particular the VTA dopamine neurons, serve several functions in the
reward system
The reward system (the mesocorticolimbic circuit) is a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), associative learning (primarily positive reinforcement and cl ...
,
motivation
Motivation is the reason for which humans and other animals initiate, continue, or terminate a behavior at a given time. Motivational states are commonly understood as forces acting within the agent that create a disposition to engage in goal-dire ...
,
cognition
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thoug ...
, and drug
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
, and may be the focus of several
psychiatric disorders. The VTA has also been shown to process various types of
emotion
Emotions are mental states brought on by neurophysiological changes, variously associated with thoughts, feelings, behavioral responses, and a degree of pleasure or displeasure. There is currently no scientific consensus on a definition. ...
output from the
amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex v ...
, where it may also play a role in avoidance and fear-conditioning.
Electrophysiological recordings have demonstrated that VTA neurons respond to novel stimuli, unexpected rewards, and reward-predictive sensory cues. The firing pattern of these cells is consistent with the encoding of a reward expectancy error.
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. Nest sharing behavior is associated with increased V1aR expression in the VTA of newly paired zebra finches.
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.
Presence of gap junctions
The VTA has been shown to have a large network of
GABAergic
In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...
neurons that are interconnected via
gap junctions. This network allows for electrical conduction, which is considerably faster than the chemical conduction of signals between synapses, though less spatially precise.
Neural composition
The VTA, like the
substantia nigra, is populated with
melanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amin ...
-pigmented
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...
rgic neurons. Recent studies have suggested that dopaminergic neurons comprise 50-60% of all neurons in the VTA, which is contrary to previous evidence that noted 77% of neurons within the VTA to be dopaminergic.
In addition, there is a sizable population of GABAergic neurons in the
rostromedial tegmental nucleus The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the ve ...
(RMTg), a functionally distinct brain structure.
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
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
, the
nucleus accumbens, and the
locus coeruleus
The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.
The locus coer ...
. The VTA also contains a small percentage of excitatory
glutamatergic neurons.
Limbic loop
The “limbic loop” is very similar to the direct pathway motor loop of the
basal ganglia
The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
. In both systems, there are major excitatory inputs from the cortex to the striatum (accumbens nucleus), the midbrain projects neuromodulatory dopamine neurons to the striatum, the striatum makes internuclear connections to the pallidum, and the pallidum has outputs to the thalamus, which projects to the cortex, thus completing the loop. The limbic loop is distinguished from the motor loop by the source and nature of the cortical input, the division of the striatum and pallidum that process the input, the source of the dopaminergic neurons from the midbrain, and the thalamic target of the pallidal output.
The ''limbic loop'' controls
cognitive
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...
and
affective
Affect, in psychology, refers to the underlying experience of feeling, emotion or mood.
History
The modern conception of affect developed in the 19th century with Wilhelm Wundt. The word comes from the German ''Gefühl'', meaning "feeling."
...
functioning and the motor loop controls movement.
CA3 loop
Linking context to reward is important for reward seeking. In 2011, a group of researchers documented a
CA3-VTA connection that uses the
lateral septum as an intermediary. They used a
pseudo-rabies virus (PRV) as a transsynaptic tracer, and injected it into the VTA. They found that unilateral injection into the VTA resulted in bilateral PRV labeling in CA3 beginning 48 hours after injection. Lesions of the caudodorsal lateral septum (cd-LS) before VTA PRV injection resulted in significantly less PRV labeled neurons in CA3.
Theta wave stimulation of CA3 resulted in increased firing rates for dopamine cells in the VTA, and decreased firing rates for GABA neurons in the VTA. The identity of VTA neurons was confirmed by neurobiotin™ labeling of the recording neuron, and then histological staining for
tyrosine hydroxylase (TH). Temporary inactivation of CA3 via GABA agonists prevented context induced reinstatement of lever pressing for intravenous
cocaine
Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...
.
The authors propose a functional circuit loop where activation of glutamatergic cells in CA3 causes activation of GABAergic cells in cd-LS, which inhibits GABA interneurons in the VTA, releasing the dopamine cells from the tonic inhibition, and leading to an increased firing rate for the dopamine cells.
Reward system
The dopamine reward circuitry in the human brain involves two projection systems from the ventral midbrain to the nucleus accumbens-
olfactory tubercle complex. First, the posteromedial VTA and central linear raphe cells selectively project to the
ventromedial striatum, which includes the medial olfactory tubercle and the medial
NAC shell. Second, the lateral VTA projects largely to the ventrolateral striatum, which includes the
NAC core, the medial NAC shell, and the lateral olfactory tubercle. These pathways are called the meso-ventromedial and the meso-ventrolateral striatal dopamine systems, respectively. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed behavior than the lateral projection system. Unlike the lateral part, the medial one is activated not by rewarding but by noxious stimuli.
Therefore, the NAC shell and the posterior VTA are the primary areas involved in the reward system.
Clinical significance
Disorders
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. The close proximity of these two pathways causes them to be grouped together under dopaminergic projections. Several disorders result from the disruption of these two pathways:
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, and
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD). 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.
Drug addiction
The nucleus accumbens and the ventral tegmental area are the primary sites where
addictive drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...
s act. The following are commonly considered to be addictive:
cocaine
Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...
,
alcohol,
opioids
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
,
nicotine,
cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
,
amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
, and their analogs. These drugs alter the neuromodulatory influence of dopamine on the processing of reinforcement signals by prolonging the action of dopamine in the nucleus accumbens or by stimulating the activation of neurons there and also in the VTA. The most common drugs of abuse stimulate the release of dopamine, which creates both their rewarding and the psychomotor effects. Compulsive drug-taking behaviors are a result of the permanent functional changes in the mesolimbic dopamine system arising from repetitive dopamine stimulation. Molecular and cellular adaptations are responsible for a sensitized dopamine activity in the VTA and along the mesolimbic dopamine projection in response to drug abuse. 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.
Experiments in rats have shown that they learn to press a lever for the administration of
stimulant drugs into the posterior VTA more readily than into the anterior VTA. Other studies have shown that microinjections of dopaminergic drugs into the nucleus accumbens shell increase locomotor activity and exploratory behaviors, conditioned approach responses, and anticipatory sexual behaviors.
The
withdrawal
Withdrawal means "an act of taking out" and may refer to:
* Anchoresis (withdrawal from the world for religious or ethical reasons)
* '' Coitus interruptus'' (the withdrawal method)
* Drug withdrawal
* Social withdrawal
* Taking of money from ...
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.
Comparative anatomy and evolution
All studies since 1964 have emphasized the impressive general similarity between the VTA of all mammals from rodents to humans. These studies have focused their efforts on rats, rabbits, dogs, cats, opossum, non-human primates, and humans. There have been slight differences noted, such as changes in the dorsal extent of the A10 cells. To be specific, the dorsal peak of A10 cells is more extensive in primates when compared to other mammals. Furthermore, the number of dopaminergic cells in the VTA increases with phylogenetic progression; for instance, the VTA of the mouse contains approximately 25,000 neurons, while the VTA of a 33-year-old man contains around 450,000 cell bodies.
See also
*
Phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...
*
List of regions in the human brain
The human brain anatomical regions are ordered following standard neuroanatomy hierarchies. Functional, connective, and developmental regions are listed in parentheses where appropriate.
Hindbrain (rhombencephalon)
Myelencephalon
*M ...
References
Further reading
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{{DEFAULTSORT:Ventral tegmental area
Midbrain
Addiction
Dopamine