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 even 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 by 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 functions, especially 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 amphetamines) which seem to be directly or indirectly related to the increase of 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 mechanisms of cocaine and amphetamine are different, however. Cocaine acts as a dopamine transporter blocker, competively inhibiting dopamine uptake to increase the lifetime of dopamine. On the other hand, amphetamines act as dopamine transporter substrates to competitively inhibit dopamine uptake and increase the dopamine efflux via a dopamine transporter.

However, the idea that dopamine is the 'reward chemical' of the brain, a view held by many during early stages of its research, 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.

However, the above theories are based on correlational, rather than causal, experimental evidence. Importantly, the available experimental evidence which examined causal, rather than corrleational, relationships between dopamine and motivation, does not seem to agree with any of above theories. For example, pharmacological blockade of brain dopamine receptors increases, rather than decreases, the rate of drug taking behavior. The theories viewing dopamine as the mediator of 'desire/wanting,' 'predicting pleasurable activity,' 'noticeableness' or "decision making" can not adequately explain this experimental evidence. Thus, the functional role of dopamin in motivation remains to be the topic of controvercy.

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, 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.

Major Dopamine Pathways
mesocortical pathway mesolimbic pathway nigrostriatal pathway tuberoinfundibular pathway