A chemical compound (catecholamine) widely distributed in the brain and peripheral nervous system, a substance from which noradrenaline and adrenaline are formed, and a central nervous system transmitter. It is a hormone which inhibits the secretion of prolactin, and promotes the release of growth hormone from the front lobe of the pituitary gland. Dopamine is a base for the synthesis of two other neurotransmitters: adrenaline and noradrenaline. Abnormal levels of dopamine in some parts of the brain are associated with particular diseases, eg, an excess is associated with schizophrenia and a deficiency with Parkinson's disease. Parkinson's disease is treated with L-dopa, which is converted to dopamine in the brain. Dopamine transmission in a part of the brain known as the nucleus accumbens is associated with drug addiction.
In the brain, dopamine functions as a neurotransmitter, activating dopamine receptors.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.
Biochemistry
Dopamine has the chemical formula (C6H3(OH)2-CH2-CH2-NH2).
As a member of the catecholamine family, dopamine is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline) in the biosynthetic pathways for these neurotransmitters.
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. Uptake back to the presynaptic neuron via the dopamine transporter is the major role in the inactivation of dopamine neurotransmission.
Functions in the brain
Dopamine has many functions in the brain.
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.
Cognition and frontal cortex
In the frontal lobes, dopamine controls the flow of information from other areas of the brain.
Regulating prolactin secretion
Dopamine is the primary neuroendocrine regulator of the secretion of prolactin from the anterior pituitary gland.
Motivation and pleasure
Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate a person proactively to 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.
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. 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. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
Recent research suggests that the firing of dopamine neurons is a motivational chemical as a result of reward-anticipation. This is based on evidence 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.
Clues to dopamine's role in motivation, desire and pleasure have come from studies performed on animals.
In humans, though, drugs that reduce dopamine activity (e.g., antipsychotics) have been shown to reduce motivation as well as cause anhedonia (the inability to experience pleasure). (The Snaith-Hamilton-Pleasure-Scale (SHAPS), introduced in English in 1995, assesses self-reported anhedonia in psychiatric patients.)
Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability(liking). Libido can be increased by drugs that affect dopamine but not by drugs that affect opioid peptides or other neurotransmitters.
Sociability is also closely tied to dopamine neurotransmission. This is also credited to an increase in dopamine, because mania alleviates from dopamine blocking antipsychotics.
Other theories reinforce that the crucial role of dopamine may be in desire, or anticipating pleasurable activity.
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 a chemical desire but as 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 receiving treatment for it.
Links to psychosis
Disruption to the dopamine system has also been strongly linked to psychosis and schizophrenia. 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.
Depression
Dopamine is a neurotransmitter that is involved in depression. Amphetamines and dopamine reuptake blockers have potent anti-depressant effects but these drugs quickly lose their benefit after they deplete dopamine levels in the brain.
Therapeutic use
Levodopa is a dopamine precursor used to treat Parkinson's disease.
Dopamine is also used as an inotropic drug in patients with shock to increase cardiac output and blood pressure.
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