The Nervous System · Part One · How It Is Built and Fueled
Lesson 06 / 61
Dopamine and the Monoamines: From Tyrosine to the Receptor That Reads It
Where the cells sit, how far the signal spreads, and when it ends.
Dopamine is a catecholamine transmitter that biases circuits instead of commanding them. Most of its release sites form no synapse, so it spreads through a volume of tissue and changes the terms for every cell inside. Which receptor subtype waits at an address decides whether gain there rises or falls, and the local transporter sets how long the change lasts. The Unified Model of Tone reads dopamine's standing level as tone held in one chemistry, which is why its loss reaches movement, hormone output, and blood pressure at once.
Precursor
Tyrosine to L-DOPA to dopamine
Cell groups
9 dopamine groups, 4 named pathways
Receptors
D1 and D5 via Gs, D2 to D4 via Gi
Cleared by
DAT and NET uptake, then MAO and COMT
Dopamine
A catecholamine transmitter built from the amino acid tyrosine in brain neurons and in the adrenal medulla. It is also the raw material for the other two catecholamines, since the same molecule is converted onward to norepinephrine and then to epinephrine. Of the three, dopamine is the most important transmitter in the central nervous system, norepinephrine second, and epinephrine barely at all.
Tonic and phasic release
Dopamine arrives in two forms at once. Firing produces brief transients lasting milliseconds. Underneath sits a standing extracellular level that persists for minutes to hours and sets how loudly each transient registers. Drugs, assays, and symptoms track these two quantities separately, and most single measurements catch only one.
01Tyrosine to dopamine
Dopamine is built by a four-enzyme chain whose first step is a regulated gate
Dopamine begins as tyrosine, a dietary amino acid. Tyrosine hydroxylase converts tyrosine to L-DOPA, and aromatic amino acid decarboxylase converts L-DOPA to dopamine. Tyrosine hydroxylase is the rate-limiting enzyme of the whole catecholamine pathway, and it requires tetrahydrobiopterin and molecular oxygen to run Daubner 2011. Dopamine supply therefore rests on a cofactor and on oxygen delivery before anything the neuron decides.
That first enzyme is itself under control. Its amino-terminal 150 amino acids form a regulatory domain, phosphorylated by several kinases at four separate serine residues and dephosphorylated by two phosphatases Daubner 2011. Dopamine binds the enzyme in competition with tetrahydrobiopterin, so the product restrains its own manufacture.
The chain does not stop at dopamine. Dopamine beta-hydroxylase, located inside the secretory vesicle, converts dopamine to norepinephrine. In the adrenal medulla the cytosolic enzyme phenylethanolamine N-methyltransferase converts norepinephrine to epinephrine. The compartment decides the product: a molecule that stays in the vesicle becomes a different transmitter from one that reaches the cytosol.
Remove the first enzyme and only some of dopamine's work fails
Deleting dopamine synthesis from dopaminergic neurons costs movement and learning but leaves pituitary control intact. Mice engineered to lack tyrosine hydroxylase in dopaminergic cell types, with the noradrenergic system rescued, show reduced spontaneous locomotion, cataleptic behavior, and failure of active avoidance learning Nishii 1998. Pituitary hormone production and secretion under hypothalamic dopaminergic control were maintained despite the defective synthesis.
Synthesis capacity is a setting the neuron carries before any input arrives. Four phosphorylation sites, two phosphatases, and a cofactor requirement mean one cell makes different amounts of the same transmitter in different states. The Unified Model of Tone counts that standing capacity as part of what the tissue is already holding.
02Findings
What the research shows
Measured values for dopamine's cell counts, spread, clearance, and reserve.
03Nine dopamine cell groups
Dopamine reaches the whole brain from a few hundred thousand cells, sorted by where their axons end
The mammalian brain holds nine dopamine-containing cell groups, mapped first by histofluorescence and then by immunohistochemistry against tyrosine hydroxylase Björklund 2007. In the brain, dopamine is produced in hypothalamic neurons, in neurons of the ventral tegmental area, and in the substantia nigra. From these nuclei run the mesolimbic, nigrostriatal, and mesocortical pathways, along with the tuberoinfundibular pathway connecting the hypothalamus to the pituitary.
The source population is small and countable. Unbiased stereology in seven human control brains at post-mortem found an average of 550,000 pigmented neurons in one substantia nigra, alongside 260,000 non-pigmented neurons Pakkenberg 1991. In seven patients with Parkinson's disease the pigmented count was reduced by 66 percent. The non-pigmented count fell only 24 percent, so the disease selects within the nucleus as well as within the brain.
Each pathway carries the same molecule to a different job. The nigrostriatal pathway carries motor command into the striatum. The mesolimbic and mesocortical pathways serve motivation and frontal regulation. The tuberoinfundibular pathway governs pituitary output. Lose the cells of one pathway and movement falters while the others run untouched.
The geography of loss defines Parkinson's disease
Pigmented nigral neurons fall at 4.7 percent per decade through normal aging, measured across 36 human control brains at post-mortem, and that loss concentrates in the dorsal tier Fearnley 1991. Aging nearly spares the lateral ventral tier, taking 2.1 percent per decade. Parkinson's disease attacks exactly that tier, removing 91 percent of it on average. It removes cells exponentially where aging removes them linearly, with 45 percent of nigral neurons gone in the first decade of illness.
Calculated loss in the lateral ventral tier at the moment symptoms begin is 68 percent, implying a presymptomatic phase of about five years Fearnley 1991. Aging and disease remove the same class of cell in a different order. In this model the order is what counts, because which part of a population goes decides what the system can no longer hold.
Pituitary dopamine works by being withdrawn
Hypothalamic dopamine reaches the pituitary through hypophysial portal blood from several nerve tracts, and those tracts are regulated by prolactin itself, by estrogens, and by several neuropeptides Ben-Jonathan 2001. Dopamine binds type-2 receptors on pituitary lactotrophs and suppresses their high intrinsic secretory activity, along with prolactin gene expression and lactotroph proliferation. Dopamine here is a standing brake, and its removal rather than its release is the signal that lets hormone output rise.
04Volume transmission
Dopamine is broadcast into a volume of tissue instead of delivered to one cell
Most dopamine release sites form no synapse. Classical anatomy gives the synaptic cleft as 20 to 40 nanometers of gap between two committed partners. Electron microscopy of adult rat neostriatum found 60 to 70 percent of dopamine varicosities asynaptic, with only 30 to 40 percent carrying a synaptic membrane differentiation Descarries 1996. Among the junctions that do form, 67 percent contact dendritic branches, 30 percent contact spines, and 2 to 3 percent contact cell bodies. The authors proposed that a basal level of extracellular dopamine is maintained permanently around every constituent of the tissue.
Distance follows from that arrangement. A diffusion model built on region-specific rat parameters at 37 degrees puts the effective dopamine radius after one quantal release at about 2 micrometers for low-affinity receptors. For high-affinity receptors it reaches 7 to 8 micrometers Rice 2008. Those spheres of influence encompass tens to thousands of synapses. Perisynaptic transporters do not gate the spillover. They only shorten how long dopamine lasts once it has already spread, and striatal uptake runs 200 times faster than uptake in the substantia nigra pars compacta.
A single monoaminergic neuron arborizes into hundreds of thousands of release sites. Complete single-axon reconstructions of eight rat nigral dopamine neurons showed each striatal axon bush covering 0.45 to 5.7 percent of total neostriatal volume, mean 2.7 plus or minus 1.5 percent Matsuda 2009. The arborizations crossed both striosome and matrix compartments, so one cell broadcasts into two territories usually treated as separate.
The cost of that arborization is why these cells fail first
A biology-based computational model of the human substantia nigra pars compacta neuron estimates more than 1 million synapses on an axon exceeding 4 meters in total length, almost all of it unmyelinated Pissadaki 2013. In that model the energy cost of propagating an action potential and restoring the membrane rises with arbor size as a power law. That puts these cells at a distinct disadvantage in energy balance, and it is one account of their selective vulnerability in Parkinson's disease. The arborization that gives one cell regional reach is what makes it fragile.
The Unified Model of Tone reads volume transmission as a level applied to a region. Dopamine changes the terms inside that region, and every synapse there computes differently for as long as the level holds.
05Receptors and reuptake
The receptor waiting for dopamine decides whether a circuit's gain rises or falls
Dopamine acts through at least five distinct G-protein-coupled receptor subtypes. D1 and D5 couple to Gs and activate adenylyl cyclase. D2, D3, and D4 inhibit adenylyl cyclase and activate potassium channels Missale 1998. No dopamine receptor gates an ion channel directly, which is what places dopamine in the metabotropic class and keeps it out of fast point-to-point signaling. It shifts the gain of a whole circuit, upward at one address and downward at another.
The same subtypes work outside the brain. Dopamine receptors participate in sodium handling in the kidney, in vascular tone in the circulation, and in hormone secretion at the pituitary Missale 1998. One transmitter family reaches motor, limbic, and cortical targets inside the brain. Outside it the same five proteins serve the kidney, the vessels, and the pituitary.
Reuptake decides how long the signal lasts
Released dopamine is largely reabsorbed intact by a specific transporter. Deleting that transporter in mice leaves dopamine in the extracellular space at least 100 times longer Giros 1996. The same animals are indifferent to cocaine and amphetamine, which lose all effect on locomotor activity and on dopamine release and uptake once the transporter is gone.
Which transporter does the work depends on the region. In synaptosomes from mouse caudate and nucleus accumbens, uptake depends primarily on the dopamine transporter, and the norepinephrine transporter blocker nisoxetine inhibits it by only 20 percent. In frontal cortex synaptosomes, dopamine uptake depends primarily on the norepinephrine transporter, and cocaine's ability to inhibit that uptake falls 70 percent in mice lacking it Morón 2002.
A few percent of transporter occupancy moves the whole state
Occupying half the striatal transporters takes far more cocaine than it takes to change how a person feels. PET with [11C]beta-CIT measured striatal transporter occupancy after intravenous cocaine, and in monkey a high dose of 7 milligrams per kilogram produced 50 percent occupancy Farde 1994. The dose that produces arousal in people is 0.25 to 0.5 milligrams per kilogram, more than ten times lower, which led the authors to infer that arousal follows occupancy of only a few percent. Compounds that jam reuptake elevate mood and produce addiction by changing a clearance rate, without adding any signal of their own.
In this model, a small change in clearance producing a large change in state is the signature of a modulatory system. The circuit was already running. Reuptake decided the level it ran at.
06Tonic dopamine bias
The monoamines set a standing bias that decides how strongly a circuit answers its inputs
Dopamine release into subcortical regions runs through two independent mechanisms. Transient phasic release follows dopamine neuron firing. A sustained background tonic release sits beneath it, regulated by prefrontal cortical afferents, and it sets the responsivity of the whole system to phasic signals Grace 1991. Grace advanced the arrangement as a hypothesis for the etiology of schizophrenia: a prolonged fall in prefrontal activity lowers tonic release, and the homeostatic compensation that follows makes each later transient land too hard.
Glutamate and GABA push and pull moment to moment. The monoamines set the level those pushes act on, layering slow chemical context over fast synaptic traffic. Dopamine and its relative serotonin together tune arousal, motivation, and motor control, and the standing bias they hold decides how vigorously a circuit answers what arrives. Tone, in this reading, is partly a chemical level the monoamines maintain.
One molecule slows a rhythm and steadies it at the same time
All five dopamine receptor subtypes are present in the spinal cord, and dopamine biases the locomotor central pattern generator directly. In the isolated neonatal mouse cord, bath-applied dopamine above 35 micromolar slowed a locomotor rhythm evoked by serotonin and N-methyl-DL-aspartic acid and made it more regular, independently of the baseline frequency Sharples 2015. The D1-like receptor contributed to the enhanced stability, the D2-like family produced the pronounced slowing, and quinpirole, the D2-like agonist, enhanced stability as well.
Two receptor families read the same molecule at the same bath concentration and pull on different properties of the rhythm, one on its speed and one on its regularity. A modulator sets the terms a circuit runs on. The cord makes the rhythm; dopamine decides how fast and how regular it is.
A11 neurons fire in proportion to how hard the body was touched
The diencephalic A11 system provides the sole dopaminergic innervation of the hindbrain and spinal cord Reinig 2017. Calcium imaging in GCaMP7a-transgenic zebrafish larvae showed anterior subgroups whose response magnitude is tuned to tactile stimulus intensity, with the lateral line identified as the source. Posterior tubercular neurons were predominantly sensory driven. Caudal and dorsomedial hypothalamic neurons fired after vigorous tail movements and stayed active for about 10 seconds.
These neurons also project onto peripheral mechanosensory systems as feedback. Somatic input sets descending dopaminergic activity, and descending dopaminergic activity sets what the periphery reports next. The loop has no first term, which is why this model treats the standing dopaminergic level and the quality of mechanical input as one quantity read at two places.
07Clearing dopamine
Clearance rate is a control variable for dopamine, and it differs from person to person
Most catecholamine metabolism happens inside the same cells that made the transmitter Eisenhofer 2004. Vesicular stores sit in a highly dynamic equilibrium, with passive outward leakage of catecholamines into the cytoplasm counterbalanced by active inward transport through vesicular monoamine transporters. A molecule is broken down mainly because it leaked out of a vesicle, and release into the cleft is only one of the routes to an enzyme.
Two enzyme families do the dismantling. Monoamine oxidase exists as two mitochondrial-bound isoenzymes, A and B Bortolato 2008. They catalyze the oxidative deamination of serotonin, norepinephrine, dopamine, and the trace amines. The reaction yields hydrogen peroxide, ammonia, and aldehydes, so clearance is chemically expensive. Catechol-O-methyltransferase runs the other route, and both convert dopamine to inactive products. The major end metabolite is homovanillic acid, formed through the intermediate DOPAC, and together they index dopamine turnover.
Monoamine oxidase inhibitors are effective antidepressants, and inhibitor development produced clinical breakthroughs running from mood disorders to Parkinson's disease Bortolato 2008. Blocking an enzyme that ends a signal changes a whole behavioral state, which makes breakdown rate a control variable.
Clearance capacity differs by genotype
Catechol-O-methyltransferase is the key enzyme eliminating dopamine in the human prefrontal cortex, and its capacity varies between people. Across 108 post-mortem human prefrontal samples, the common Val158Met variant significantly affected COMT protein abundance and enzyme activity while leaving messenger RNA unchanged Chen 2004. The Val allele was the predominant factor determining higher prefrontal COMT activity, and by inference lower synaptic dopamine. Two people with identical release hold different standing levels of the transmitter.
Losing one degradative enzyme changes behavior
In one large human kindred, five affected males carried a point mutation in the eighth exon of the MAOA structural gene Brunner 1993. The mutation changes a glutamine codon to a termination codon and abolishes MAO-A activity. Synthesis and release were intact. Twenty-four-hour urine testing showed markedly disturbed monoamine metabolism, and the phenotype included disturbed regulation of impulsive aggression. The lifespan of the signal, on its own, was enough to change behavior.
Turnover tracks the cardiovascular set-point
Jugular venous sampling with the Fick principle measured subcortical monoamine turnover in 15 untreated patients with essential hypertension and 32 healthy controls. Subcortical HVA overflow ran at 0.5 plus or minus 0.2 nanomoles per minute in the hypertensives against 2.1 plus or minus 0.5 in controls, an inverse relationship with blood pressure Lambert 1994. MHPG overflow, indexing norepinephrine turnover, ran the other way at 1.4 against 0.5 nanomoles per minute, and it correlated with total-body norepinephrine spillover.
Two arms of one chemical family moved in opposite directions in the same subcortical tissue, and blood pressure moved with them. The Unified Model of Tone reads that reciprocal pattern as one organization read at two chemistries, which is why a figure for brain monoamine turnover indexes blood pressure at all.
08Dopamine reserve and threshold
The size of a dopamine reply depends on the state the input meets
Hard exercise does not raise striatal dopamine in people. Twelve volunteers ran on a treadmill for 30 minutes, raising heart rate by 143 plus or minus 47 percent above rest, and PET with [11C]raclopride found no change in synaptic dopamine. The putamen-to-cerebellum distribution volume ratio, the measure of D2 receptor availability, was 4.22 plus or minus 0.34 after running against 4.17 plus or minus 0.29 at baseline Wang 2000. Rat microdialysis shows exercise raising striatal dopamine, and the human measurement did not reproduce it.
A large somatic input met a striatal system already sitting inside its working range, and the level did not move. That is what a buffered modulatory system does. The size of a dopamine reply is set by where the receiving state already sits, and vigorous exercise does not flood the striatum with the transmitter.
The same depletion produces different states
Progressive MPTP lesioning in macaques, built up slowly over months, placed the symptom threshold at 43.2 percent loss of tyrosine-hydroxylase-positive nigral neurons. At that same point striatal transporter binding had fallen 80.3 percent and striatal dopamine content 81.6 percent Bezard 2001. Increased dopamine metabolism did not act as an efficient early compensation, and D2-like binding fell before it rose. Roughly four fifths of striatal dopamine went missing before the first motor sign appeared.
A second primate series found far less headroom. Fifteen macaques received randomized unilateral doses of the same toxin and were scored by blinded validated ratings. A loss of 14 to 23 percent of nigral neuron counts, or 14 to 37 percent of striatal dopamine, was enough to induce mild parkinsonism Tabbal 2012. Residual cell count correlated with parkinsonism score at r equals -0.87. The link between score and residual striatal dopamine held linearly until nigral loss passed 50 percent, after which further loss stopped registering on the scale.
Both figures are real, and the distance between them is the finding. They were not made the same way. Bezard scored the first motor sign as a lesion accumulated over months. Tabbal scored mild parkinsonism after single randomized doses. The spread reflects how the lesion arrived and how early the deficit was called, not one series being wrong. This model claims the reserve threshold as a property of the system's standing organization, not a fixed percentage of dopamine. The same measured depletion then produces a different clinical state depending on how the rest of the network is set. Parkinson's disease is where those depletion figures are read as clinical instrument values.
Somatic input reaches the dopamine system directly
We are the practice organized around the nervous system, and this is the point of contact. A11 hypothalamic neurons take graded mechanical information as their input: in zebrafish larvae their response magnitude is tuned to tactile stimulus intensity, and they stay active about 10 seconds after vigorous movement Reinig 2017. That system is the sole dopaminergic supply to the hindbrain and cord, so mechanical input of the kind care delivers lands on the dopaminergic machinery itself.
The Unified Model of Tone reads all of this as one quantity. What a dopaminergic input accomplishes is decided by two things the receiving tissue already holds: which receptor subtype waits at the address, and how fast the local transporter clears the molecule. Held inside its range, that arrangement absorbs a large disturbance without moving, which is what the treadmill result shows. Driven outside it, the same arrangement loses the room to absorb anything, and a depletion that one nervous system carries silently produces parkinsonism in another.
The commitment is testable in this chemistry. If receptor subtype and clearance rate set the size of a dopamine reply, two people with the same measured depletion should differ in symptom by however much their receptor complement and their COMT capacity differ. A somatic input should move the standing level only where that level has already drifted from its range. A finding that depletion alone predicted the clinical state would leave this account with nothing to explain. Tone carries the general form of the commitment.
Two people with identical release hold different standing levels of the transmitter.
09Tone
How this system expresses tone
Every part of the nervous system expresses all of tone. In the dopamine system three foundations are directly measurable.
Gain
D1 and D5 raise adenylyl cyclase at one address while D2 to D4 lower it at another. One molecule moves a circuit's gain in either direction.
Set point
The nigrostriatal system defends a range. Motor signs followed 43.2 percent nigral neuron loss in one primate series and 14 to 23 percent nigral loss in another.
Time course
Clearance decides the signal's lifespan. Deleting the dopamine transporter in mice leaves dopamine in the extracellular space at least 100 times longer than normal.
The remaining foundations are visible in dopamine's own numbers. Oscillation: brief phasic transients ride on a sustained background level, and dopamine above 35 micromolar slows and regularizes the locomotor rhythm of the isolated neonatal mouse cord. Prediction: prefrontal afferents regulate the tonic level, so the cortex biases how much each transient will count before it arrives. Load: more than 1 million synapses on 4 meters of largely unmyelinated axon make these among the most expensive cells in the brain to keep polarized. Constraint: a cell answers dopamine only if it carries a receptor for it, and D1-like and D2-like families push adenylyl cyclase in opposite directions. Input quality: A11 hypothalamic neurons in zebrafish larvae are tuned to tactile stimulus intensity and stay active about 10 seconds after vigorous movement. Coupling: subcortical HVA overflow ran four times lower in untreated hypertensives while norepinephrine turnover ran nearly three times higher, one reciprocal movement read at two chemistries.
10Across the library
How this page relates to the rest of the library
Where dopamine's chemistry is read across the rest of the library.
The wider transmitter families, and why the receptor at the far side of the cleft decides the reply for every one of them.
The circuit the nigrostriatal pathway biases, where D1-like and D2-like receptors sit on separate output pathways and push adenylyl cyclase in opposite directions.
What movement looks like once nigrostriatal output falls past its reserve, which one primate series placed at 43.2 percent nigral cell loss.
The other monoamine arm, built from tryptophan instead of tyrosine and cleared by the same monoamine oxidase isoenzymes.
Why monoamine oxidase yielding hydrogen peroxide matters, and what an energy-disadvantaged cell with 4 meters of axon does under oxidative load.
The depletion figures read as clinical instrument values: what a dopamine transporter scan reports, and why the symptom threshold is a range from 14 to 43 percent instead of a single number.
11Frequently asked
Questions about this topic
What does dopamine do in the brain?
Dopamine biases circuits rather than commanding them. It acts through at least five G-protein-coupled receptor subtypes, with D1 and D5 activating adenylyl cyclase and D2, D3, and D4 inhibiting it and opening potassium channels. No dopamine receptor gates an ion channel directly, so the transmitter shifts the gain of a whole circuit. Its axons reach the striatum for movement, the limbic system and frontal cortex for motivation and regulation, the pituitary for hormone control, and the spinal cord, where dopamine slows and steadies the locomotor rhythm.
Where is dopamine made, and how?
Dopamine is synthesized from the amino acid tyrosine. Tyrosine hydroxylase converts tyrosine to L-DOPA using tetrahydrobiopterin and molecular oxygen, and aromatic amino acid decarboxylase converts L-DOPA to dopamine. Tyrosine hydroxylase is the rate-limiting enzyme of the whole catecholamine pathway, and its 150 amino acid regulatory domain carries four serine phosphorylation sites, so supply is adjustable. The mammalian brain holds nine dopamine-containing cell groups, principally the substantia nigra, the ventral tegmental area, and dopaminergic neurons of the hypothalamus. One human substantia nigra holds about 550,000 pigmented neurons.
What are the four dopamine pathways?
The nigrostriatal pathway carries motor command from the substantia nigra into the striatum. The mesolimbic and mesocortical pathways run from the ventral tegmental area and serve motivation and frontal regulation. The tuberoinfundibular pathway runs from the hypothalamus to the pituitary, where dopamine reaches lactotrophs through portal blood and suppresses prolactin secretion, prolactin gene expression, and lactotroph proliferation. One transmitter reaches motor, limbic, cortical, and endocrine targets from a handful of midbrain and hypothalamic cell groups, and the sorting is done entirely by where the axons end.
How is dopamine cleared after it is released?
Released dopamine is largely reabsorbed intact by the dopamine transporter, though in frontal cortex the norepinephrine transporter handles most of the uptake. Deleting the dopamine transporter in mice leaves dopamine in the extracellular space at least 100 times longer. Enzymatic breakdown then follows, mostly inside the cells that made the transmitter, through monoamine oxidase A and B or through catechol-O-methyltransferase. The major end metabolite is homovanillic acid, formed through DOPAC, and homovanillic acid levels are used to index dopamine turnover in tissue and blood.
Why do Parkinson's symptoms appear so late?
Dopamine carries a reserve, though its size is disputed. In progressive MPTP-lesioned macaques, motor signs appeared only after 43.2 percent loss of tyrosine-hydroxylase-positive nigral neurons and 81.6 percent loss of striatal dopamine content. Human post-mortem morphometry shows the disease attacking the lateral ventral tier of the substantia nigra, which normal aging nearly spares. Loss of that tier reaches 68 percent at symptom onset, implying a presymptomatic phase near five years. A second primate series found mild parkinsonism after only 14 to 23 percent nigral loss.
How does cocaine affect dopamine?
Cocaine blocks the dopamine transporter, the protein that reabsorbs released dopamine and ends the signal. Mice lacking that transporter show no locomotor response to cocaine or amphetamine at all, which makes the transporter an obligatory target. PET imaging in monkey found that 7 milligrams per kilogram of intravenous cocaine occupies 50 percent of striatal transporters. The human arousal dose is 0.25 to 0.5 milligrams per kilogram, more than ten times lower, so arousal follows occupancy of only a few percent of the same transporters.
Is dopamine the reward chemical?
Dopamine is a modulator with several addresses, and reward is one of them. The same molecule sets motor bias in the striatum and restrains prolactin release at the pituitary. It handles sodium in the kidney, affects vascular tone, and slows the locomotor rhythm generated in the spinal cord. Most of its release sites form no synapse, so it reaches tissue by diffusion into a volume that can encompass thousands of synapses. What dopamine accomplishes at any one site is decided by the receptor subtype waiting there.
How does the Unified Model of Tone read dopamine?
The Unified Model of Tone claims that dopamine's reserve is a property of the whole system's standing organization. Two things the receiving tissue already holds set the size of any reply: which receptor subtype waits at the address, and how fast the local transporter clears the molecule. The same measured depletion therefore produces different clinical states depending on how the rest of the network is set. That is what the two primate threshold series found, and it is why a chemical assay on its own describes a person poorly.
12The sources
References
Sources: primary literature, linked inline.