Dopamine
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Dopamine

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. more...

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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 brain 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.

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 dehydration 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

Role in movement

Dopamine is critical to the way the brain controls our movements and is a crucial part of the basal ganglia motor loop. 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.

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Dopamine gene ups schizophrenia risk
From Science News, 11/5/05

The chances of developing schizophrenia rise substantially for the small number of children who possess only one copy of a gene variant that regulates a crucial chemical messenger in the brain, according to a new finding of a long-term investigation.

A team led by psychiatrist Allan L. Reiss of Stanford University School of Medicine studied 24 children missing a small piece of DNA on chromosome 22. About 30 percent of youngsters with this deletion, which occurs in 1 in 4,000 births, eventually develop the severe mental disorder schizophrenia or related psychotic conditions. These children are also prone to other problems, including heart defects, cleft palate, and learning disorders.

Prior studies showed that people with this deletion lack one copy of the usual two copies of the COMT gene, which triggers production of a protein that breaks down the neurotransmitter dopamine. The protein comes mainly in two variants with contrasting dopamine-busting power, one weak and the other strong.

By young adulthood, seven of the study participants with the deletion had developed schizophrenia or another psychotic disorder, Reiss and his coworkers report in the November Nature Neuroscience. Of that number, the four individuals with the weak COMT variant--who presumably grew up with excessive amounts of dopamine in their brains--displayed larger drops in verbal intelligence and language skills, and harsher psychotic symptoms, than their three peers with the strong variant did. Also, the prefrontal brain area of the four participants with the weak variant shrank more than did that area in three participants with the strong variant. This brain region is linked to schizophrenia.

COMT-associated dopamine drenching of children's growing brains creates a strong susceptibility to schizophrenia, Reiss proposes. He also hypothesizes that a dopamine drought in children who inherit a single copy of the strong COMT variant can also foster psychotic symptoms.--B.B.

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