Dopamine
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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 drug which 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, a synthetic precursor to dopamine such as L-DOPA can be given, since this will cross the blood-brain barrier.
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Biochemistry
Dopamine.png
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 is a neurotransmitter as well.
Dopamine is synthesized in the body (mainly nervous tissue and adrenal glands) 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-package 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 function, particularly those linked to memory, attention and problem solving. This function is particularly related to the mesocortical dopamine pathway.
Role in Pleasure and Motivation
Dopamine is commonly associated with the 'pleasure system' of the brain, providing feelings of enjoyment and reinforcement to motivate us to do, or continue doing, certain activities. Certainly 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 amphetamine) which seem to directly or indirectly related to increase dopamine in these areas, and in relation to neurobiological theories of addiction, which argue that these dopamine pathways are pathologically altered in addicted persons. The mechanism of cocaine and amphetamine is different. Cocaine is acting as dopamine transporter blocker to competively inhibit dopamine uptake to increase the lifetime of dopamine, while amphetamine is acting as a dopamine transporter substrate to competively inhibit dopamine uptake and increase the dopamine efflux via dopamine transporter.
However, the idea that dopamine is the 'reward chemical' of the brain now seems too simple as more evidence has been gathered. Dopamine is known to be released when unpleasant or aversive stimuli are encountered, suggesting that it is not only associated with 'rewards' or pleasure. Also, the firing of dopamine neurons occurs when a pleasurable activity is expected, regardless of whether it actually happens or not. This suggests that dopamine may be involved in desire rather than pleasure. Drugs that are known to reduce dopamine activity (e.g. antipsychotics) have been shown to reduce people's desire for pleasurable stimuli, despite the fact that they will rate them as just as pleasurable when they actually encounter or consume them. It seems that these drugs reduce the 'wanting' but not the 'liking', providing more evidence for the desire theory.
Other theories suggest that the crucial role of dopamine may be in predicting pleasurable activity. Related theories argue that dopamine function may be involved in the salience ('noticeableness') of perceived objects and events, with potentially important stimuli (including rewarding things, but also things which may be dangerous or a threat) appearing more noticeable or more important. This theory argues that dopamine's role is to assist decision making by influencing the priority of such stimuli to the person concerned.
Dopamine and Psychosis
Disruption to the dopamine system has also been strongly linked to psychosis and schizophrenia. 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, all modern antipsychotic medication is designed to block dopamine function to varying degrees.
See the article on the dopamine hypothesis of psychosis for a wider discussion of this topic.
Major Dopamine Pathways
See also
- addiction
- amphetamines
- antipsychotic
- catecholamine
- catechol-O-methyl transferase
- cocaine
- dopamine hypothesis of schizophrenia
- neurotransmitter
- Parkinson's disease
- schizophrenia
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