Dopamine

Dopamine is a monoamine neurotransmitter that belongs to the catecholamine family; the catecholamine family includes dopamine, norepinephrine, and epinephrine.

Mainly produced in the nervous system and adrenal medulla; it plays a role in many brain functions like behavior and cognition.

A naturally occurring endogenous catecholamine that stimulates beta1-and alpha1-adrenergic and dopaminergic receptors in a dose-dependent fashion.

Dopamine is the primary neurotransmitter of the reward system in the brain. 

Dopamine neurons are thought to be involved in learning to predict which behaviors will lead to a reward such as food or sex.

Dopamine helps regulate movements, emotion, cognition, motivation, and feelings of pleasure.

Natural rewards, like eating, and recreational drug use cause a release of dopamine, that reinforce these stimuli.

Nearly all addictive drugs, directly or indirectly, act upon the brain’s reward system by heightening dopaminergic activity.

Many recreational drugs, such as cocaine, mimic this reward response—providing an explanation for their addictive nature.

It is suggested that dopamine neurons fire when a reward is greater than that previously expected; a key component of reinforcement learning.

Excessive intake of many types of addictive drugs result in high amounts of dopamine, which in turn affects the reward pathway directly through heightened dopamine receptor activation. 

Prolonged, high levels of dopamine in the synaptic cleft can induce receptor downregulation in the neural pathway: and can result in a decrease in the sensitivity to natural rewards.

It stimulates the release of norepinephrine.

In low doses (2-5 μg/kg/min), dopamine acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilatation in these beds.

In midrange doses (5-15 μg/kg/min), it acts on beta-adrenergic receptors to increase heart rate and contractility.

In high doses (15-20 μg/kg/min), it acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise blood pressure.

The plasma reference ranges for dopamine are:

Supine adults – < 10 ng/ml (conventional units); < 0.065 nmol/L (SI units)

Ambulatory adults – < 20 ng/mL (conventional units); < 0.13 nmol/L (SI units)

Age 3-15 years – < 60 pg/mL (conventional units); < 0.39 nmol/L (SI units)

Age Conventional Units SI Units

3-8 y 80-378 µg/24 h 523-2472 nmol/24 h

9-12 y 51-474 µg/24 h 334-3100 nmol/24 h

13-17 y 51-645 µg/24 h 334-4218 nmol/24 h

17 y 52-480 µg/24 h 340-3139 nmol/24 h

The activity of dopaminergic neurons declines during aging.

Catecholamines including dopamine may be elevated in the following instances:

After a medication withdrawal such as clonidine, or alcohol.

In acute illness

With medications such as tricyclic antidepressants, buspirone, antipsychotic agents, cocaine, Levodopa.

Antipsychotic drugs such as haloperidol and chlorpromazine tend to block dopamine D2 receptors in the dopaminergic pathways of the brain. 

Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences. 

Decreased dopamine release in the prefrontal cortex, and excess dopamine release in other pathways, are associated with psychotic episodes in schizophrenia and bipolar disorder.

Tyrosine hydroxylase converts tyrosine to 3,4-dihydroxyphenylalanine (DOPA), which is converted to dopamine under the effect of aromatic l-amino acid decarboxylase.

Dopamine β-hydroxylase converts dopamine to norepinephrine and phenylethanolamine N -methyltransferase converts norepinephrine to epinephrine.

Plasma and/or urine dopamine tests are indicated as part of the work up for:

Pheochromocytoma

Paraganglioma

Neuroblastoma

Plasma and/or urine dopamine can be used in the monitoring of the following conditions:

Adrenal incidentaloma

Neuroblastoma after therapy

Plasma fractionated catecholamines includes plasma dopamine, epinephrine, and norepinephrine, whereas 24-hour urine fractionated catecholamine includes urine dopamine, epinephrine, and norepinephrine.

The most acceptable approach for pheochromocytoma diagnosis is to screen with 24-hour urine collection for fractionated metanephrines and catecholamines; if high clinical suspicion exists, then plasma fractionated metanephrines should then follow as a confirmatory test.

During the work-up for neuroblastoma, dopamine, whether in the urine or the plasma, should be measured in combination with 24-hour urine vanillylmandelic acid (VMA) and homovanillic acid (HVA).

The use of low-dose dopamine for the treatment of acute renal failure does not prevent mortality, acute renal failure, or need for dialysis and should be eliminated from routine clinical use.

Dopamine stimulates dopaminergic receptors and proportionally has a greater increase in splanchnic and renal perfusion and may facilitate resolution of lung edema(Bertollo AM).

Dopaminergic stimulation can alter the hypothalamus-pituitary function with a decrease in prolactin levels and growth hormone levels.

Dopamine and norepinephrine have different effects on the kidney, splanchnic vessels, and the pituitary axis.

Either dopamine or norepinephrine can be used as the first agent for vasopressor effect in patients with shock.

Some studies show that the administration of dopamine may be associated with higher death rates than those associated with the administration of norepinephrine with septic shock (Martin C, Boulain T).

In a randomized multicenter controlled study in patients with shock that received dopamine or norepinephrine as first line vasopressor therapy to restore and maintain blood pressure:there was no difference in the death rate between the two gents, but the use of dopamine was associated with a greater number of adverse events, especially arrhythmias (De Backer D).

Acute CHF patients with renal impairment treated with low dose dopamine or low dose nesiritide did not improve congestion or renal function (The ROSE Acute Heart Failure Randomized Trial).

Refers to the immediate metabolic precursor of norepinephrine.

Occurs naturally in the CNS in the basal ganglia, where it functions as a neurotransmitter, as well as in the adrenal medulla.

Can activate α- and βadrenergic receptors.

At higher doses, it can cause vasoconstriction by activating α1 receptors, whereas at lower doses, it stimulates β1 cardiac receptors.

Dopamine is a neurotransmitter that acts on D1 type (D1 and D5) Gs coupled receptors, which increase cAMP and PKA, and D2 type (D2, D3, and D4) receptors, which activate Gi-coupled receptors that decrease cAMP and PKA.

Dopamine is connected to mood and behavior, and modulates both pre and post synaptic neurotransmission.