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Dopamine Receptor SNPs: Addiction, Mood, ADHD, and Schizophrenia

Key takeaways:
~Dopamine is a powerful player in our cognitive function – impacting mood, movement, and motivation.
~ Excess dopamine – or – not having enough dopamine can cause mental and physical changes.
~Genetic variants in the dopamine receptors influence addiction, ADHD, neurological diseases, depression, psychosis, and aggression.

This article covers information on neurotransmitters related to psychiatric health.  If you are under psychiatric care, talk with your doctor before making any changes.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today 

Dopamine: Neurotransmitter for motion and emotion

Dopamine acts as a neurotransmitter in the brain, transmitting a signal from one neuron to the next. It is a monoamine neurotransmitter, classified as a catecholamine.  A monoamine just means that it contains a single amine group – and this is important in the way that it is regulated in the brain.

Dopamine is derived from the amino acid tyrosine, which is converted to L-dopa and then to dopamine.

Dopamine is involved in:

  • Movement
  • Reward
  • Memory
  • Lactation
  • Attention
  • Sleep regulation

The dopamine molecule acts on dopamine receptors to cause motion and emotion.

Motion: 
Dopamine is important in how the brain controls movement, and it needs to be balanced. Too much dopamine leads to more movement – such as tics and involuntary movement. Too little dopamine leads to less movement – such as in Parkinson’s.

Emotion:
Dopamine is also important in emotions. Excess dopamine leads to euphoria, hallucinations, and psychosis. Dopamine causes conditioning – for example, learning either not to do something (via punishment) or learning to do something through reward. Not enough dopamine leads to anhedonia – that feeling of not caring about anything.

Prolactin:
Dopamine also functions within the hypothalamus and pituitary gland to affect hormones. Specifically, dopamine inhibits prolactin. Without enough dopamine, it can lead to amenorrhea (lack of periods) in women and impotence and gynecomastia (moobs) in males.

Where is dopamine made?

There are two small regions deep in the brain where dopamine is made:

  • the substantia nigra
  • the ventral tegmental area

From there, it travels via tracts to other areas of the brain.

Dopamine Receptors: Understanding the different effects of dopamine

Dopamine doesn’t do anything by itself – it needs to bind with a receptor to cause an action. There are five different dopamine receptors in humans, coded for by the DRD1 through DRD5 genes. These G-protein coupled receptors receptors are responsible for the slightly different effects of dopamine in various brain regions as well as different tissues throughout the body.

DRD1 receptor:

The most abundant dopamine receptor in the brain is DRD1. It is found in several regions of the brain, including the neostriatum, basolateral amygdala, cerebral cortex, hypothalamus, and thalamus.

The DRD1 receptor is linked to the effects of alcohol consumption. Blocking the DRD1 gene decreases alcohol-seeking behavior in animal studies. It also decreases heroin and cocaine-seeking behavior.[ref]

Working memory – short-term memory needed for thinking and speaking – depends on the DRD1 receptors in the prefrontal cortex. Interestingly, working memory is considered to have a strong genetic component based on the DRD1 gene variants.[ref]

DRD2 receptor:

The DRD2 receptor is less abundant in the cerebral cortex than the DRD1 receptors, but it is abundant in other areas of the brain with dopaminergic neurons.

Both agonists and antagonists of the DRD2 receptor have been shown in animal studies to decrease alcohol and opiate consumption. The studies show that higher levels of either an agonist (something that stimulates the receptor) or antagonist (something that blocks the receptor) alter the addictive response.[ref]

DRD3 receptor:

The DRD3 receptor is found in the ventral striatum and other limbic areas in the brain. In humans, there are low amounts of DRD3 receptors found in the cortical regions. This differs from other species and is a good reminder that animal studies may not be totally applicable to humans.[ref]

The DRD3 receptor has a higher affinity for dopamine (>20-fold higher than DRD2 receptors). This means that dopamine is more likely to bind with the DRD3 receptors, and high levels of dopamine will prompt the brain to make more DRD3 receptors. The ability to change with fluctuating dopamine levels makes the DRD3 receptor critical in dopamine-related functions and cognition.[ref]

DRD4 receptor:

This dopamine receptor is found at lower levels than DRD1 through DRD3. It is found in the retina, cerebral cortex, amygdala, hypothalamus, and pituitary. The DRD4 receptor likely doesn’t play a role in alcohol, opiate, or cocaine addiction.[ref]

DRD5 receptor:

The DRD5 receptor is very similar to the DRD1 receptor, and they are often located together. There seems to be a lot more research on DRD1, but often substances that bind to DRD1 also bind to DRD5.[ref]

Dopamine and Addiction:

Addiction to drugs causes compulsive drug-seeking behavior. The dopamine system is involved in the rewarding effects of drugs, and a lot of addictive drugs increase dopamine levels in certain regions of the brain. In fact, it has been known since the 1990s that blocking dopamine transmission takes away the reward effects of some addictive substances, such as cocaine and amphetamines.[ref]

There are three theories on how dopamine is related to addiction. First, the extra dopamine produced by addictive substances trains the brain through the reward system. It is the idea that the brain learns to like the drug, or makes it a habit. The second theory is that addictive substances change the brain’s circuits, making them hypersensitive. Third, researchers theorize that there is an imbalance between dopamine and other neurotransmitters. [ref]

Mental disorders associated with abnormal dopamine levels:

Several diseases are associated with altered dopamine.

  • Tics / Tourettesexcess striatal dopamine due to GABAergic network dysfunction[ref]
  • Psychosis – excess dopamine
  • Schizophrenia – excess dopamine in some areas of the brain (causes hallucinations) and not enough in others[ref][ref]
  • Addiction – caused in part by repeated surges in dopamine (reward) and increased dopamine receptors
  • ADHD -associated with low dopamine function in certain areas of the brain[ref]
  • Bipolar affective disorder –  high dopamine during mania which elevated DRD2 and DRD3 receptors, coupled with reduced dopamine during depression[ref]
  • Anorexia – decreased reward (dopamine) for food along with other neurotransmitter imbalances (such as histamine)[ref]
  • Depression – low dopamine is seen in people with inflammation-associated depression.[ref]

Additionally, Parkinson’s disease is caused by not enough dopamine due to degradation of the dopamine-producing area of the brain (substantia nigra).

Related article: ADHD Genes

Connections between dopamine levels and inflammation:

Neuroinflammation in dopaminergic neurons causes cell death and a reduction in dopamine. This is thought to be the cause of Parkinson’s disease.[ref]

Tetrahydrobiopterin (BH4) is needed for the synthesis of dopamine. Pro-inflammatory cytokines reduce the production of BH4, thus potentially reducing dopamine levels in situations of systemic inflammation.[ref]

” Dopaminergic neurotransmission is very sensitive to inflammation. At the periphery, the production of neopterin and nitric oxide during inflammation consumes tetrahydrobiopterin to the detriment of the hydroxylase enzymes that use this compound as a cofactor”.[ref]


Dopamine Receptor Genotype Report:

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Lifehacks:

Again, let me caution that you don’t want to experiment with your neurotransmitters if you are under psychiatric care without talking with your doctor. Read the research and talk with your doctor or health care practitioner.

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Related Genes and Topics:

Serotonin Genes
Serotonin is a neurotransmitter that is important in depression, sleep, and many other aspects of health. Learn how genetic variants in the serotonin receptor genes impact their function.

COMT Gene
Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. The COMT gene codes for the enzyme catechol-O-methyltransferase which breaks down (metabolizes) the neurotransmitters dopamine, epinephrine, and norepinephrine.

 

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.