Dopamine quick review

• Hormone description: a derivative of the amino acid tyrosine, a monoamine neurotransmitter formed in the brain by the decarboxylation of dopa.

• Biological functions: responsible for fundamental brain functions, activates dopamine receptors, inhibits the release of prolactin from the anterior lobe of the pituitary.

• Health benefits: useful in the control of movement, the formation of emotional responses, and the perception of pain and pleasure, shortage of dopamine causes Parkinson's disease.

• Side effects : excessive dopamine in the limbic system and not enough in the cortex may produce an overly suspicious personality giving to bouts of paranoia or may inhibit social interaction.

Dopamine

Dopamine is a derivative of the amino acid tyrosine. Dopamine is produced by neurons located in a part of the brain called the Substantia Nigra (Black Substance), whichis part of the Basal Ganglia (a group of structures in the midbrain). Dopamine is a monoamine neurotransmitter formed in the brain by the decarboxylation of dopa and essential to the normal functioning of the central nervous system. Tyrosine is modified by tyrosine hydroxylase to form dopa. Dopa decarboxylase then removes carbon dioxide from dopa to for dopamine. Monoamines are a class of neurotransmitters which also include serotonin and norepinephrine (or noradrenaline). Dopamine then serves as a precursor to norepinephrine and epinephrine. Dopamine, as well as norepinephrine and epinephrine, is packaged in granulated vesicles to be transmitted across the synapse. The neurotransmitter dopamine is found throughout the hypothalamus both in cell bodies and in axons originating from intra- and extrahypothalamic sources. 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 functions

Dopamine is responsible for fundamental brain functions. Dopamine dendrites extend into various regions of the brain, controlling different functions through the stimulation of α and β adrenergic and dopaminergic receptors. Dopamine is a neurotransmitter that affects a wide variety of brain processes, many of which are involved in the control of movement, the formation of emotional

responses, and the perception of pain and pleasure. 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.

Dopamine is a sympathomimetic catecholamine which exhibits alpha adrenergic, beta adrenergic, and dopaminergic agonism. Dopamine is the immediate metabolic precursor of norepinephrine and adrenaline. Dopamine can have either an excitatory or inhibitory effect on the postsynaptic potential. When dopamine leaves the presynaptic neuron and goes into the synapse, it can then bind to receptors on the postsynaptic neuron. After dopamine is bound to the postsynaptic cell, it can either facilitate an action potential or inhibit it. A neuron that classically releases dopamine is called a dopaminergic neuron. A series of neurons that are connected by synapses forms a pathway called a dopaminergic pathway. Neurons that make dopamine are damaged in Parkinson's disease, and the symptoms of the disease are caused by dopamine lack.

Dopamine plays a significant role in the cardiovascular, renal, hormonal, and central nervous systems. Dopamine is useful in the management of states of low cardiac output, associated with compromised renal function as with cardiogenic and hypovolemic shock. Dopamine also causes the release of norepinephrine from nerve terminals, which contributes to its effects on the heart. Dopamine usually increases the systolic and pulse pressure and either has no effect on the diastolic blood pressure or increases it slightly. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. Aside from controlling movement, dopamine is also greatlyinvolved in feelings of reward and alertness and purposeful behavior.

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 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 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 trasnportet substrate to competively inhibite dopamine be uptaken and increase the dopamine efflux via dopamine transporter.

Dopamine deficiency and Parkinson's disease

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. Parkinson's disease is a movement disorder associated with aging, characterized by progressive loss of nerve cells in a deep part of the brain called the midbrain. Cells in the midbrain that are lost in Parkinson's disease use the chemical messenger dopamine. Dopamine works by stimulating receptors on the surface of corpus striatum cells. Drugs which also stimulate these receptors are called dopamine agonists. Dopamine agonists can induce an antiparkinsonian effect through actions on either D1-like or D2-like dopamine receptors, and the multiple receptor subtypes present in the brain may provide further opportunities to improve the treatment of Parkinson's disease.

Dopamine and psychosis

Disruption to the dopamine system has also been strongly linked to psychosis and schizophrenia. Dopamine moves into frontal lobe regulating flow of information coming in from other areas of the brain. Compromise in the flow of dopamine may cause disrupted or incoherent thought as in schizophrenia. Schizophrenia is most commonly characterized by both 'positive symptoms' (those additional to normal experience and behaviour) and 'negative symptoms' (the lack or decline in normal experience or behaviour). Positive symptoms are grouped under the umbrella term psychosis and typically include delusions, hallucinations, and thought disorder. Negative symptoms may include inappropriate emotional displays or flat emotional affect, poverty of speech, and lack of motivation. Certain drugs, such as cocaine, block the return of dopamine into the brain, resulting in a build up of dopamine in the synapse, leading to drug-induced psychosis or schizophrenia.

Contraindications, interactions, precautions, side effects

Dopamine is hypersensitive to sympathomimetic amines and sulfites. Use with caution in patients with persistent pulmonary hypertension of the newborn. Once returned to the sending neuron by the reuptake system, dopamine is subject to an enzyme named monoamine oxidase (MAO). Inhibition of this enzyme prolongs and potentiates the effect of dopamine. Reserpine prevents the reuptake of dopamine and some other neurotransmitters. Administering reserpine causes dopamine to remain exposed within the cell and broken down by MAO. This profoundly reduces the available dopamine. Acidosis decreases effectiveness of dopamine. Dopamine effects are prolonged and intensified by betablockers. Excessive dopamine into the frontal lobe lessens pain and increases pleasure. In milder disorders, too much dopamine in the limbic system and not enough in the cortex may produce an overly suspicious personality giving to bouts of paranoia or may inhibit social interaction.