Mirror of English Wikipedia, the free encyclopedia

For other uses, see Dopamine (disambiguation).

Dopamine
General
Systematic name	4-(2-aminoethyl)benzene-1,2-diol
Other names	2-(3,4-dihydroxyphenyl)ethylamine; 3,4-dihydroxyphenethylamine; 3-hydroxytyramine; DA; Intropin Revivan
Molecular formula	C8H11NO2
SMILES	C1=CC(=C(C=C1CCN)O)O
Molar mass	153.18 g/mol
Appearance	white powder with distinctive smell
CAS number	[51-61-6]
Properties
Density and phase	? g/cm3, ?
Solubility in water	? g/100 ml (? °C)
Melting point	128 °C (401 K)
Boiling point	? °C (? K)
Acidity (pKa)	?
Basicity (pKb)	?
Chiral rotation [α]D	?°
Viscosity	? cP at ? °C
Structure
Molecular shape	?
Coordination geometry	?
Crystal structure	?
Dipole moment	? D
Hazards
MSDS	External MSDS
Main hazards	?
NFPA 704	?
Flash point	? °C
R/S statement	R: 36/37/38 S: 26-36
RTECS number	UX1088000
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Related compounds
Other anions	?
Other cations	?
Related ?	?
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Dopamine is a chemical naturally produced in the body. In the brain, dopamine functions as a neurotransmitter, activating dopamine receptors. Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.

Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, since dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and Dopa-Responsive Dystonia, a synthetic precursor to dopamine such as L-DOPA can be given, since this will cross the blood-brain barrier.

Contents 1 Biochemistry 2 Functions of dopamine in the brain 2.1 Role in movement 2.2 Role in cognition and frontal cortex function 2.3 Role in regulating prolactin secretion 2.4 Role in Motivation and Pleasure 3 Dopamine and psychosis 4 Therapeutic use 5 Major dopamine pathways 6 See also 7 External links 8 References 9 Notes

Biochemistry

Dopamine has the chemical formula (C₆H₃(OH)₂-CH₂-CH₂-NH₂). Its chemical name is 4-(2-aminoethyl)benzene-1,2-diol and it is abbreviated "DA."

As a member of the catecholamine family, dopamine is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline) in the biosynthetic pathways for these neurotransmitters. Arvid Carlsson won a share of the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor to these, but a neurotransmitter as well.

Dopamine is synthesized in the body (mainly by nervous tissue and adrenal glands) first by the hydration of the amino acid tyrosine to DOPA by tyrosine hydroxylase and then by the decarboxylation of DOPA by aromatic-L-amino-acid decarboxylase. In neurons, dopamine is packaged after synthesis into vesicles, which are then released in response to the presynaptic action potential. The inactivation mechanism of neurotransmission are 1) uptake via a specific transporter; 2) enzymatic breakdown; and 3) diffusion. Uptake back to the presynaptic neuron via the dopamine transporter is the major role in the inactivation of dopamine neurotransmission. The recycled dopamine will face either breakdown by an enzyme or be re-packaged into vesicles and reused.

Functions of dopamine in the brain

Dopamine has many functions in the brain. Most importantly, dopamine is central to the reward system. Well-founded research on this topic can be found on http://www.pdn.cam.ac.uk/staff/schultz/. Dopamine neurons may have the role to emit a teaching signal for prioritizing and learning of reward-directed behaviour and to code reward information relative to established predictions.

Role in movement

Dopamine affects the basal ganglia motor loop which in turn affects the way the brain controls our movements. Shortage of dopamine, particularly the death of dopamine neurons in the nigrostriatal pathway, causes Parkinson's disease, in which a person loses the ability to execute smooth, controlled movements.

Role in cognition and frontal cortex function

In the frontal lobes, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive functions, especially memory, attention and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder and negative schizophrenia.

Role in regulating prolactin secretion

Dopamine is the primary neuroendocrine regulator of the secretion of prolactin from the anterior pituitary gland. Dopamine produced by neurons in the arcuate nucleus of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the median eminence, which supply the pituitary gland. The lactotrope cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion.

Role in Motivation and Pleasure

Image:Stop hand.svg

The neutrality of this article or section may be compromised by "weasel words". Please see the relevant discussion on the talk page

Image:Stop hand.svg

The neutrality and factual accuracy of this article are disputed. Please see the relevant discussion on the talk page.

Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate proactively perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens and striatum) by naturally rewarding experiences such as food, sex, use of certain drugs and neutral stimuli that become associated with them. This theory is often discussed in terms of drugs (such as cocaine and amphetamines), which seem to be directly or indirectly related to the increase of dopamine in these areas, and in relation to neurobiological theories of chemical addiction, arguing that these dopamine pathways are pathologically altered in addicted persons. However, cocaine and amphetamine influence separate mechanisms of action.

Cocaine is a dopamine transporter blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150%) within the parameters of the dopamine neurotransmitters. ^[1]

Like cocaine, amphetamines increase the concentration of dopamine in the synaptic gap, but by a different mechanism. Amphetamines are similar in structure to dopamine, and so can enter the terminal button of the presynaptic neuron via its dopamine transporters as well as by diffusing through the neural membrane directly. When entering inside the presynaptic neuron, amphetamines force the dopamine molecules out of their storage vesicles and expel them into the synaptic gap by making the dopamine transporters work in reverse. ^[2]

However, the idea that dopamine is the 'reward chemical' of the brain, a view held by many during early stages of its research, is contradicted by evidence that suggests dopamine is not a 'reward chemical', but a 'desire' or 'motivational chemical'. Dopamine is released when unpleasant or aversive stimuli are encountered, and so motivates towards the pleasure of avoiding or removing the unpleasant stimuli.

Recent research suggests that the firing of dopamine neurons is a motivational chemical as a result of reward-anticipation. This is based on evidence^{[citation needed]} that, when a reward is perceived to be greater than expected, the firing of certain dopamine neurons increases, which correspondingly increases desire or motivation toward the reward.

Dopamine's role in motivation and desire comes from studies performed on animals.^{[citation needed]} It has been shown experimentally that when the dopaminergic system of a rat is selectively abolished it will stop eating, possibly because it is no longer motivated towards the pleasure of food. When the rat is force fed food it will still display the proper facial expressions which indicate whether they like or dislike it. The conclusion is that while a lack of dopamine prevents the rat from desiring the pleasure of food, it does not prevent the rat from experiencing the pleasure of eating the food.

In the inverse, when dopamine is in abundance, mutant hyperdopaminergic mice show higher desire of food but not a higher pleasure in enjoying the food.¹ This research^{[citation needed]} was taken to mean that dopamine controls motivation and desire instead of pleasure. In humans, drugs that reduce dopamine activity (e.g., antipsychotics) have been shown to induce reduced motivation (lack of desire) as well as anhedonia (inability to experience pleasure, possibly because of a lack of anticipation).²

The selective D2/D3 agonists pramipexole and ropinirole have pro-motivational and anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale.³ Opioid and cannabinoid transmission instead of dopamine is believed to be what modulates food reward and palatability (enjoying food).⁴ This explains why animals still have the same enjoyment of food conpletely independent of brain dopamine concentrations. Other desires are likely dependent on dopamine. Libido can be increased by drugs that increase dopamine secretion, but not by drugs that affect opioid peptides or other neurotransmitters.

Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor binding is found in people with social anxiety. Traits common to negative schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar, manic subjects can become hypersocial as well as hypersexual. This is also credited to an increase in dopamine, because mania alleviates from dopamine blocking antipsychotics.

Other theories reinforce^{[citation needed]} that the crucial role of dopamine may be in desire, or anticipating pleasurable activity. Related theories^{[citation needed]} argue that dopamine function may be involved in the salience ('noticeableness') of perceived objects and events, with potentially important stimuli such as: 1) rewarding things or 2) dangerous or threatening things ~ seeming more noticeable or important. This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.

Pharmacological blockade of brain dopamine receptors increases rather than decreases drug-taking behavior. Since blocking dopamine decreases desire, the increase in drug taking behavior may be seen as not as a chemical desire but a deeply psychological desire to just 'feel something'.

Deficits in dopamine levels are implicated as one of several possible causes for Adult attention-deficit disorder (AADD), and some types of medications used to treat Attention-deficit hyperactivity disorder (ADHD/ADD) will help to stimulate dopaminergic systems, leading to potentially heightened sensation, for those afflicted by it and are receiving treatment for it.

Dopamine and psychosis

Disruption to the dopamine system has also been strongly linked to psychosis and schizophrenia. ^[3] Dopamine neurons in the mesolimbic pathway are particularly associated with these conditions. This is partly due to the discovery of a class of drugs called the phenothiazines (which block D₂ dopamine receptors) that can reduce psychotic symptoms, and partly due to the finding that drugs such as amphetamine and cocaine (which are known to greatly increase dopamine levels) can cause psychosis. Because of this, most modern antipsychotic medication is designed to block dopamine function to varying degrees. Blocking the D₂ dopamine receptor is known to cause relapse in patients that have achieved remission from depression, and such blocking also counteracts the effectiveness of SSRI medication.

See the article on the dopamine hypothesis of psychosis for a wider discussion of this topic.

Therapeutic use

Please expand this article. This template may be found on the article's talk page, where there may be further information. Alternatively, more information might be found at Requests for expansion. Please remove this message once the article has been expanded.

Levodopa is a dopamine precursor used to treat Parkinson's disease. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa or benserazide. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used. These include entacapone and tolcapone.

Dopamine is also used as an inotropic drug in patients with shock to increase cardiac output and blood pressure.

Major dopamine pathways

• Mesocortical pathway
• Mesolimbic pathway
• Nigrostriatal pathway
• Tuberoinfundibular pathway

See also

• Addiction
• Amphetamine
• Antipsychotic
• Catecholamine
• Catechol-O-methyl transferase
• Cocaine
• Dopamine hypothesis of schizophrenia
• Dopamine reuptake inhibitors
• Methylphenidate
• Neurotransmitter
• Parkinson's disease
• Prolactinoma
• Schizophrenia
• Selegiline
• Freedom of thought

External links

CID 681 from PubChem

• DrugBank APRD00085

References

1. ^ Melissa Hoegler (Url accessed 06-07-06). Cocaine in the Brain.
2. ^ Amphetamines. Canadian Institues of Health Research: (Url accessed 06-07-06).
3. ^ Disruption of gene interaction linked to schizophrenia. St. Jude Children's Research Hospital: (Url accessed 06-07-06).

Notes

1. ↑ Pecina S, Cagniard B, Berridge KC, Aldridge JW, Zhuang X.(2003) Hyperdopaminergic mutant mice have higher "wanting" but not "liking" for sweet rewards.J Neurosci. 23(28):9395-402.
   
2. ↑ Lambert M, Schimmelmann BG, Karow A, Naber D.(2003) Subjective well-being and initial dysphoric reaction under antipsychotic drugs - concepts, measurement and clinical relevance.Pharmacopsychiatry., Nov;36 Suppl 3:S181-90.
   
3. ↑ Matthias R. Lemke, M.D., H. Michael Brecht, M.D., Juergen Koester, Ph.D., Peter H. Kraus, M.D. and Heinz Reichmann, M.D.(2005) Anhedonia, Depression, and Motor Functioning in Parkinson’s Disease During Treatment With Pramipexole. J Neuropsychiatry Clin Neurosci. 17:214-220.
   
4. ↑ Susana Peciña and Kent C. Berridge .(2005) Hedonic Hot Spot in Nucleus Accumbens Shell: Where Do µ-Opioids Cause Increased Hedonic Impact of Sweetness?J Neurosci. 25(50):11777-11786.