Basal ganglia are the oldest structure in your brain, one that has been coordinating movement, motivation, and reward for some 560 million years. Read on to find out how it works, what can go wrong, and how to help keep it running smoothly.
What Are the Basal Ganglia?
The basal ganglia are a group of specialized brain cells located deep in the middle of the brain. Their most important roles are to orchestrate movement, regulate feelings of reward, and govern other instinctual needs. These are very old functions and concerns on the evolutionary time scale: the basic structure of the basal ganglia has been the same for almost all of vertebrate evolution [1, 2].
The largest structure in the basal ganglia, the striatum (composed of the caudate, putamen, and nucleus accumbens in the image above), receives signals from parts of the brain using dopamine. It then sends out new signals using GABA .
Your Reptilian Brain
One interesting theory from the 60s gave rise to the popular concept of the reptilian brain. While most scientists were focusing on the conscious, thinking brain, the neuroscientist Paul MacLean set out to understand the structures that underlie our more primitive, unconscious actions. “Instinct has been kind of a dirty word for some time”, he announced back then .
MacLean coined the term “Triune Brain”. He was also the first to come up with the term limbic system, which we frequently use today. According to the triune model, your brain is divided into 3 layers or parts :
- The reptilian brain or your basal ganglia, the most primitive part of the brain that governs balance and where your basic instincts reside
- The limbic system or the old mammalian brain, which governs your emotions, social behavior, and some aspects of memory
- The neocortex, or the human brain, which directs complex processes like language, abstract thinking, advanced cognition, and planning.
It was first thought that this structure originated from ancient lizards – hence the popular reptilian brain idea. However, even the lamprey, a primitive fish used to model some of the earliest vertebrates, uses the same basal ganglia pathways as we do to move, breathe, and swallow. So, the emergence of this part of the brain probably predates reptiles [1, 2].
As modern research has uncovered much more about the brain in the meantime, this theory has become outdated. It’s not precise, and there are several important exceptions to it. But it helped scientists initially understand some aspects of brain anatomy and behavior.
Functions of the Basal Ganglia
The basal ganglia allow us to very precisely control our movement by preventing unwanted movement.
When you decide to move a part of your body, the signal travels to a part of the basal ganglia called the caudate nucleus. This elongated C-shaped structure (see the red structure in the image below) uses the neurotransmitter GABA to send the signal to another part of the basal ganglia called the pars reticulata [1, 4].
Neurons in the pars reticulata inhibit movement. GABA is always “inhibitory”. In this case, its job is to momentarily deactivate (or pause) activity in the pars reticulata for movement to take place [1, 4].
Motivation and Decision-making
Dopamine in the basal ganglia controls motivation by encouraging feel-good sensations over unpleasant ones. Essentially, we avoid situations that result in low dopamine, and we seek to repeat situations that result in high dopamine .
This makes sense from an evolutionary perspective. If humans didn’t instinctively avoid the “down” of low dopamine, they probably wouldn’t have survived to tell the tale. Problems arise, however, once addictive drugs come into the picture. They can hijack our feedback system by overloading the basal ganglia with dopamine and creating a euphoric high .
As an extension of this function, the basal ganglia also help us make decisions. Just like the more strong-willed of us will make responsible, hard decisions when faced with a dilemma, your basal ganglia will be working on the seemingly more basic life decisions in the background. They will assign values to different possible actions based on the probability of receiving a reward .
The basal ganglia may help filter information, selecting what is and what is not important for the brain to process. Their job is to save the brain from an unnecessary burden. If they need to, they will shut off irrelevant information before it reaches your conscious brain .
Unsurprisingly – given their role in decision-making and working memory – the basal ganglia also help you learn and build habits. By reinforcing behaviors with either good or bad feelings (reward or punishment), the basal ganglia help us figure out what to do in situations we’ve encountered before [8, 6].
The reinforcement can be guised as anything from a social reaction (people frown or smile in response to your behavior), material goods (treats, toys, money), or specific events (injury, fear, pleasure, etc.)
The basal ganglia also control curiosity and the desire (or lack thereof) for new experiences .
Health Disorders Linked to Basal Ganglia Issues
If your basal ganglia come out of balance – be it from stress, psychological issues, brain damage, or more subtle triggers – many problems can arise. The symptoms and health conditions you may experience as a result depend on several complex factors such as:
- Which part of the basal ganglia is affected
- Whether other parts of the brain are damaged
- If over- or under-activity is underlying it
- Your age, sex, and genetic predispositions
- Your overall health status
…and many more.
Only a specialized health team, comprising of a neurologist, will be able to diagnose any issues with this otherwise elusive group of cells. Nonetheless, understanding the science behind the conditions its imbalance is linked to can be empowering. The purpose of this section is to help you understand this deep-seated brain structure a bit better, not to point to any diagnostic factors!
1) Huntington’s Disease
Huntington’s disease is a hereditary neurodegenerative disorder that usually surfaces in a person’s 30s or 40s. People with Huntington’s disease have problems with movement and usually develop uncontrolled writhing movements called chorea. Other common symptoms include learning difficulties and depression .
In Huntington’s, a genetic mutation causes neurons in a region of the basal ganglia called the striatum to die. These are the cells that manage movement: as they are damaged and die off, the affected person loses muscle control [11, 10].
Huntington’s disease is caused by high levels of repetition in the gene that codes for a protein called huntingtin. Researchers have yet to discover exactly why this repetition causes damage to the basal ganglia .
2) Parkinson’s Disease
Parkinson’s is another neurodegenerative disease characterized by movement problems. These include shaking and stiffness of the muscles, which leads to slow movements and difficulties with balance, speech, and writing. Sleep disorders, depression, and intellectual difficulties might also arise .
A group of basal ganglia cells called the substantia nigra, which means “black substance”, releases dopamine and helps coordinate movement. Their cell bodies are black because of a dark pigment called neuromelanin, which is formed from excess dopamine [14, 15, 16, 17].
In Parkinson’s disease, the immune system attacks these pigmented neurons: this reduces dopamine release. It blocks impulses from other parts of the brain, making the initiation of movement impossible: people with Parkinson’s have trouble beginning a movement. Damage to the basal ganglia explains the hallmark symptoms of Parkinson’s; movement problems first appear when 30 – 70% of cells in the substantia nigra have died [16, 18, 14, 15, 19].
Many people with Parkinson’s disease experience minor illusions that may progress to clear hallucinations. Hallucinations, in turn, can lead to delusional thinking. Damage to the basal ganglia can cause hallucinations and delusions after a stroke; a similar mechanism may be at work in Parkinson’s. These symptoms may also be a result of damage to different brain regions [20, 21, 22].
The exact cause of Parkinson’s is unknown, but some forms of the disease are genetic. One form of genetic Parkinson’s disease, called PARK9 or Kufor-Rakeb syndrome, sometimes presents with unusually high levels of iron in the basal ganglia .
3) Basal Ganglia Stroke
When brain cells are completely cut off from their oxygen supply, they can no longer function. After a few minutes, cells start to die: this event is called a stroke or infarction. Stroke can affect many brain regions, including the basal ganglia [23, 24].
Stroke affecting the basal ganglia usually causes movement disorders, but the precise type of disorder depends on many factors. The injury’s location, severity, and the person’s age and susceptibility may all combine and interact to determine how movement is affected .
Some disorders that may result from a basal ganglia stroke include:
- Chorea: quick, random, involuntary writhing movements of the entire body, but mainly of the feet and hands. Chorea is very common after a stroke. Ballism is closely related to it, but it’s more rare and severe. Movements originate in the upper arm and thigh [25, 26].
- Dystonia: sustained contraction of muscles, often in the hand, foot, face, and tongue. It takes almost 10 months to appear after a stroke and usually fades or disappears with time [25, 27].
- Myoclonus: sudden, irregular bursts of shaking movements similar to that of people with epilepsy [25, 28].
- Tremor: shaking, usually of the hands and arms, but all parts of the body can be affected. It is similar to myoclonus, but more rhythmic [25, 29].
- Complex movement disorders: A combination of symptoms from the more defined movement disorders in this list .
- Restless leg syndrome: an uncontrollable need to move the legs, especially at night. This syndrome is described more fully in the section below .
Reversal learning is a type of impulse control: the ability to resist taking an action that was previously rewarded. Cognitive flexibility, or the ability to adapt to new situations, is a product of reversal learning [31, 32].
People who have suffered a stroke to the basal ganglia often have reversal learning difficulties .
4) Restless Leg Syndrome
People with restless leg syndrome, or RLS, are uncomfortable when sitting or lying still and have an uncontrollable need to move their legs. Symptoms are worst in the evening and at night, which makes it difficult to fall asleep and stay asleep. Poor sleep quality decreases a person’s ability to function during the day, so RLS affects the daytime quality of life as well .
The causes of RLS are not well understood. However, the substantia nigra in the basal ganglia in RLS is altered: it has decreased iron levels and impaired dopamine activity. Furthermore, people who have suffered a stroke in the basal ganglia sometimes develop RLS [30, 25].
5) Tourette Syndrome
A person with Tourette Syndrome has tics: automatic movements, sounds, and words. These tics are technically voluntary, but they are prompted by an involuntary urge that can only be satisfied or reduced by making the tic .
Problems with the basal ganglia are likely involved in triggering Tourette. In the brains of people with this syndrome, the basal ganglia are not properly connected to the supplementary motor area, another part of the brain that controls movement .
Furthermore, the composition of the basal ganglia is changed in Tourette: certain neurons become more and others less dense, but their overall number decreases. These neurons (containing parvalbumin) stimulate the production of GABA, which normally inhibits movement. Low GABA levels from fewer brain cells in this region may play a role in the development of Tourette Syndrome [33, 34, 35].
Tics are most severe in childhood and almost always improve or disappear in adulthood. About half of children with Tourette Syndrome no longer have tics as adults .
6) Meige Syndrome
Meige syndrome is a rare disorder that provokes spasms in the eyelid muscles and uncontrollable muscle contractions in the face, jaw, and tongue. Its causes are not well-studied, but it can develop after exposure to levodopa and antipsychotic drugs that may damage the basal ganglia .
7) Wilson’s Disease
Wilson’s disease is another rare disorder that gives rise to movement problems similar to those in Parkinson’s disease. It is caused by a genetic disease defect in a liver protein that processes copper and removes it from the body. In a person with Wilson’s disease, copper builds up in the liver and basal ganglia, resulting in liver failure and difficulties with motor control [37, 38, 39].
Essentially, anxiety sets off an exaggerated fear response to threats that may not exist. People with anxiety try to avoid the situations that triggered intense fear in the past (aversive behavior), which may interfere with everyday tasks, like going to work or making an important phone call. About one in four people will suffer from an anxiety disorder in their lives [40, 41, 42].
Dysfunction in the basal ganglia can lead to anxiety disorders. The basal ganglia, among its other functions, normally processes information about rewards: it helps you recognize when something good has happened and how to repeat the experience .
The striatum is a part of the basal ganglia which is heavily involved in processing and sensing rewards. This region also organizes stimuli by their importance: it helps you pay attention to the things that are important and ignore the things that are not. In people with anxiety, the striatum may give much higher importance to both real and imaginary threats over potential rewards [44, 45].
On the other hand, the striatum also helps avoid threats, fear, and other unpleasant feelings. This response, if overactive, may help explain some aspects of anxiety, such as the avoidance of everyday tasks that can become crippling .
From this perspective, the basal ganglia in people with anxiety are making wrong judgement calls, and may be biasing your perception of reality. By judging threats to be more important than rewards, your brain will steer you to less pleasant experiences. By seeking to avoid past threats, your brain may greatly limit the situations that won’t provoke an anxious response.
The striatum and the rest of the basal ganglia change a great deal during adolescence. The fear responses you learned as a teenager are processed differently than those you learned as either a child or an adult. Changes in the basal ganglia during adolescence may be the root of some anxiety disorders. In other cases, anxiety may develop due to inflammation in the basal ganglia [44, 45, 46].
68% of people with anxiety also have another mental illness, which is unsurprising given how many mental health and brain disorders may involve the basal ganglia .
9) Mood Disorders
Depression is a surprisingly common mental illness: more than 10% of adults experience a depressive episode at least once in their lives. During these episodes, people go through negative (depressed) mood and lose interest in the things they otherwise enjoyed .
Mood disorders, including depression, may develop as a result of inflammation in the basal ganglia. Cytokines, compounds released during chronic inflammation, cause changes in the structure of the basal ganglia. They decrease the production and effectiveness of dopamine, which can cause low mood, fatigue, and other symptoms [46, 48, 49].
Dopamine in the basal ganglia helps regulate sleep. When there isn’t enough dopamine in the basal ganglia, nighttime wakefulness and insomnia – the inability to sleep – can arise. People with other mentioned conditions, especially Parkinson’s disease, often suffer from insomnia for this reason .
Weak communication between different parts of the brain may also cause insomnia. In particular, the brains of people with insomnia show weak connectivity between the amygdala and the striatum of the basal ganglia [54, 55, 56].
Attention deficit hyperactivity disorder, or ADHD, causes a variety of symptoms. These span the inability to focus, control impulses, or sit still: the ADHD triad of inattentiveness, impulsivity, and hyperactivity. ADHD is often considered a childhood disorder, but up to 65% of children still have it as adults [57, 58].
The basal ganglia may play a role in ADHD: people with ADHD have a smaller than normal striatum. As a result, they don’t produce enough dopamine. This lack of dopamine probably causes the classic ADHD symptoms triad [57, 59, 60].
Autism is a behavioral disorder with a very wide array of symptoms that range from mild to disabling. 1.68% of eight-year-old children were diagnosed with autism in the USA in 2014. Currently, the rate of autism is about 1% in both children and adults – subject to change depending on how we understand and define this disorder [61, 62, 63].
People with autism have structurally different brains. The striatum of the basal ganglia, in particular, is larger and deformed in autistic brains. These differences may explain why people with autism have difficulty predicting consequences and responding to social cues [63, 64, 65, 66].
Schizophrenia is a severe mental illness. Symptoms can include illogical thoughts, hallucinations, trouble focusing, motivation difficulties, and problems expressing emotions. Some report an inability to find joy or pleasure, similar to people with depression [67, 68].
The basal ganglia are much less active in the brains of people with schizophrenia than in healthy people. However, people with schizophrenia also appear to produce more dopamine in the striatum. Furthermore, communication between the basal ganglia and other parts of the brain is disrupted in schizophrenic brains [67, 69].
Increases in dopamine above healthy levels probably cause schizophrenic hallucinations. Meanwhile, the overall decrease in basal ganglia activity may explain the lack of focus, motivation, emotional expression, and enjoyment of activities .
14) Obsessive Compulsive Disorder
Obsessive-compulsive disorder, or OCD, is a mental health disorder marked by obsessions and compulsions. Obsessions extremely distressing unwanted, repetitive thoughts, images, urges, and fears. People will try to fight them off by taking some compulsive action, which often seems irrational or excessive .
Communication between the striatum of the basal ganglia and other parts of the brain is weakened in people with OCD. This miscommunication is similar to that in schizophrenia and depression, which suggests similar underlying problems in the brain .
When we think of addiction, we usually think of addictive substances like tobacco, alcohol, heroin, or cocaine. Substance abuse of this type is mediated by a structure in the basal ganglia called the nucleus accumbens, sometimes called the reward center [71, 72, 73].
The nucleus accumbens creates the rewarding feelings that come along with addictive drugs. This region of the basal ganglia is sensitive to dopamine, which, in short, makes you feel good. Drugs like heroin and cocaine massively increase the amount of available dopamine in your brain, stimulating the nucleus accumbens and creating the addictive high. The addiction produced by all this dopamine is so powerful that, in some studies, animals will choose cocaine over food until they starve to death [74, 72].
Over time, the nucleus accumbens becomes less sensitive to this dopamine rush and the pleasant feelings associated with the drug are no longer produced. Instead, the periods in between doses become increasingly uncomfortable and eventually painful. Taking more of the addictive substance becomes the only way to relieve this discomfort .
Substance abuse and long-term addiction can have lasting effects on people’s DNA. Cocaine, in particular, affects multiple genes in the nucleus accumbens of the basal ganglia and permanently changes glutamate pathways .
All addictions result from a stimulus, either chemical or otherwise, hijacking the nucleus accumbens and the reward pathways in the brain .
Natural Substances to Improve Basal Ganglia Function
Caffeine blocks adenosine receptors and increases the number of dopamine receptors in the striatum of the basal ganglia. It may also directly increase dopamine release in the nucleus accumbens. Together, these effects explain how coffee wakes you up and keeps you going [76, 77, 78, 79].
Through its effect on the basal ganglia, moderate amounts of caffeine might help prevent and slow down the progression of Parkinson’s disease .
Caffeine is most often consumed in coffee, but you can also find it in tea and chocolate .
On the downside, coffee (and caffeine) may cause inflammation, worsen anxiety and heart problems, contribute to inflammation, and trigger addiction. Some people are especially sensitive to its negative effects. In others, tolerance tends to develop quickly and leads people to consume more and more to get the same benefits.
The striatum of the basal ganglia contains cannabinoid receptors that are sensitive to THC and CBD. After exposure to THC, the nucleus accumbens releases dopamine. Because of this, cannabis can help treat movement disorders, such as Parkinson’s disease and Tourette Syndrome, which are caused by disrupted dopamine pathways [84, 85, 86, 87, 88].
At lower doses, THC can also reduce anxiety, possibly through its action on cannabinoid receptors in the striatum. However, at higher doses and over a long period of time, THC can decrease the overall function of the dopamine system. On the other hand, CBD lessens anxiety at all doses that have been studied and may also protect the brain from the potential negative effects of THC [89, 90, 91, 92].
The amino acid tyrosine is converted into dopamine in the brain. Tyrosine is considered a non-essential amino acid because our bodies can make it from a different amino acid, phenylalanine [93, 94, 95, 96].
Tyrosine can be taken as a supplement, but it is also available in protein-rich foods like :
- Meat (beef, lamb, pork, chicken)
- Cheese and other dairy
- Whole grains
4) Red Wine
Red wine contains a variety of chemicals with important health benefits. One chemical found in red wine, called resveratrol, may protect the striatum from losing too much dopamine in people with Parkinson’s disease [100, 101, 102].
In Huntington’s disease, resveratrol may protect the basal ganglia from dopamine toxicity. In one rat study, it also reduced addictive behaviors and prevented changes to dopamine neurons in the basal ganglia [103, 104].
5) Green Tea
Polyphenols from green tea may help with disorders affecting the basal ganglia, including anxiety, OCD, bipolar disorder, Parkinson’s disease, and movement disorders caused by stroke [107, 108, 109, 106].
Ashwagandha affects multiple neurotransmitter pathways, including the GABA and dopamine systems in the striatum. It improved symptoms in people with Parkinson’s disease and it may help with Huntington’s disease as well [111, 112, 113].
In one study, ashwagandha extract reduced behavioral symptoms and damage to the basal ganglia (striata) in rats with Parkinson’s disease .
An extract of Rhodiola rosea – also known as rose root, Arctic root, or king’s crown – may ease the symptoms of ADHD. In one study, researchers gave Rhodiola rosea extract to a group of rats and measured their brain activity, including in the striatum of the basal ganglia. They found that Rhodiola rosea extract produced similar brain changes as methylphenidate, the active ingredient in Ritalin .
Rhodiola rosea is also a promising ingredient of a natural complementary treatment for Parkinson’s disease. Extracts of Rhodiola rosea, red wine, green tea, and dwarf periwinkle, in combination, could strengthen the effects of Parkinson’s medication .
8) Sideritis scardica
Like Rhodiola rosea, an extract of Sideritis – also known as iron wort, mountain wort or shepherd’s tea – may ease the symptoms of ADHD. When researchers gave Sideritis extract to a group of rats, it produced similar brain changes as the ADHD drug methylphenidate .
9) Ginkgo biloba
In one study, ginkgo extract injections prevented the striatum from releasing too much dopamine after an injury. In another study of rats with suppressed dopamine release, ginkgo extract returned dopamine levels to near normal. These results suggest that ginkgo may generally protect nervous tissue from damage [117, 118, 119].
Ginkgo extract could help with ADHD. It may be used alone or in combination with standard ADHD treatments, but further research is required to fully understand how it works and how useful it might be .
10) Boost Your Endorphins (Natural Opioids)
Opioids target the nucleus accumbens, the part of the basal ganglia that makes you feel good in response to a reward. Opioids create the feeling of a high by causing the brain to release huge amounts of dopamine, which is processed by the nucleus accumbens [124, 72, 71].
Opioids like oxycodone can change gene expression in the basal ganglia. Research into the precise mechanism and effect of many opioids is ongoing .
We advise against any opioid drugs that have not been prescribed by your doctor. However, few people know that there are many natural, safe, and effective ways to boost your opioids, also known as endorphins and enkephalins. Some good strategies include:
- Cold exposure (cold showers or ice baths)
- High-intensity exercise
- Sleep and keeping a healthy circadian rhythm
- Sun exposure
- Massages and acupuncture 
- Acidophilus probiotics
- Low-dose naltrexone (with the guidance of a healthcare professional)
Aside from supporting your basal ganglia, boosting your natural opioids will also balance your immune system and lower inflammation. Read this article to learn more about ways to enhance your opioid system with lifestyle changes, diet, and supplements.
Effect of Drugs on the Basal Ganglia
Drugs that Increase Dopamine (+ Natural Alternatives)
1) L-Dopa and Dopamine Agonists
Levodopa, often called L-Dopa, has been used to treat Parkinson’s disease since its discovery in the 1960s. In fact, L-Dopa is so effective at decreasing the movement problems caused by Parkinson’s that a strong positive reaction to L-Dopa is used to help diagnose the disease .
The movement problems caused by Parkinson’s disease arise when dopamine levels are too low. L-Dopa is converted into dopamine in the brain, which compensates for this decrease and reduces symptoms [19, 126].
Over the course of five to ten years, L-Dopa can cause problems of its own. People who develop Parkinson’s disease earlier in life often suffer from dyskinesia, a chorea-like movement problem caused by long-term L-Dopa exposure. Because of this, early-onset Parkinson’s is usually treated with dopamine agonists for up to ten years before switching to L-Dopa .
Dopamine agonists include drugs like amantadine, which make dopamine receptors in the basal ganglia more sensitive. These sensitized receptors have an increased reaction to the decreased dopamine already present in the brain .
L-Dopa and dopamine agonists are also used to treat restless leg syndrome .
2) ADHD Medication
Methylphenidate is the active ingredient in Ritalin, Concerta, Daytrana, and some other ADHD medication. The action of methylphenidate is complicated and acts on multiple pathways in the brain. In the basal ganglia, it increases the amount of available dopamine and activates dopamine receptors. Both of these actions will intensify dopamine’s effects. This improves focus and reduces the symptoms of ADHD [127, 128].
Amphetamine is the active ingredient in Adderall. Amphetamine also has a complicated mechanism of action and, like methylphenidate, activates dopamine receptors in the basal ganglia. An increased response to dopamine improves focus in people with ADHD [129, 130].
Some antidepressants act on receptors in the striatum of the basal ganglia. For example, sertraline, the active ingredient in Zoloft, increases the amount of available serotonin and dopamine in the striatum [131, 132, 133].
Fluoxetine, the active ingredient in Prozac, protects against damage to the striatum and substantia nigra .
Maintaining healthy serotonin levels will not only improve your mood, but will also contribute to good emotional balance, happiness, and wellness. Some safe supplements that boost dopamine include l-tryptophan, 5-HTP, vitamin D (or sun exposure), probiotics, and omega-3 fatty acids. This is just the tip of the iceberg, though. If you want to dive deeper check out this post.
4) Mood Stabilizers
Mood stabilizers like valproate, carbamazepine, and lamotrigine reduce the symptoms of bipolar disorder, in part, by supporting the function of the basal ganglia and increasing available dopamine [135, 136, 137, 138].
These drugs have complex mechanisms and are also prescribed to prevent seizures. In such cases, increased dopamine in the basal ganglia can produce side effects including tremor, tics, and other movement problems [138, 139].
It’s important to know that most of these mood stabilizers (and the majority of anti-seizure drugs) also work by stimulating GABA. Changes in basal ganglia activity in people with anxiety may also be linked to GABA imbalances. On the bright side, you enhance your GABA naturally in a variety of ways. Some scientifically proven methods include the following supplements and lifestyle interventions:
- Magnolia Bark
- Lemon Balm
- Black seed oil
- Taurine 
- Magnesium 
- Vitamin B6 
- Vagus nerve stimulation
- Meditation and yoga [143, 144]
- Breathing exercises 
- Exercise, in the long run
Increasing GABA is generally beneficial for people who struggle with anxiety, high stress, irritability, and insomnia. However, since GABA is the brain’s main “brake signal”, boosting this neurotransmitter can provide you with an array of other health benefits. For example, it may even increase your emotional intelligence and help prevent depression. Uncover more about GABA in this post.
Other Drugs that Increase GABA
Benzodiazepines, or benzos, are tranquilizing drugs that act on the nucleus accumbens region of the basal ganglia .
The basal ganglia’s exact role in sleep regulation is still being studied, but the striatum contains many GABA receptors. Benzos bind to these receptors and reduce the amount of GABA required to activate them. GABA is an inhibitory neurotransmitter: it slows down brain activity, helps you relax, and regulates sleep [146, 147, 53].
Benzos also increase the amount of dopamine available to the brain: they increase how often dopamine is released but decrease the amount released each time .
Zolpidem, sold as Ambien, is used to treat insomnia and other sleeping problems and may be used to treat Parkinson’s disease. In one case study, it also improved all symptoms of Wilson disease. [151, 152, 153, 37].
Zolpidem binds to and activates the same receptors as benzodiazepines, mainly in a region of the basal ganglia called the globus pallidus .
Drugs that Block Dopamine
Tetrabenazine has a complicated mechanism, but its main action decreases the amount of dopamine in the striatum of the basal ganglia .
Antipsychotic drugs are a group of compounds used to treat a variety of psychotic disorders including schizophrenia .
Many drugs in this class block dopamine receptors in the basal ganglia, including:
Of these, risperidone also affected glutamate receptors in the basal ganglia. Some subtypes of glutamate receptor increased in response to risperidone, and some subtypes decreased .
All of the above medications except clozapine may have side effects that resemble the motor symptoms of Parkinson’s disease. Clozapine avoids this side effect because it only blocks dopamine receptors for a short time .
In one study, people taking antipsychotic drugs like risperidone to treat their schizophrenia switched to an atypical drug called olanzapine. Before the switch, these people all had basal ganglia structures up to 20% larger than normal. After the switch, their basal ganglia all returned to a normal size .
Melatonin, lithium, and 5-HT also lower dopamine activity.
Genetics of the Basal Ganglia
In Huntington’s disease, the protein huntingtin has an unusually long polyglutamine tract: a part of the protein made of only the amino acid glutamine. This long glutamine chain is caused by repetitions of the sequence CAG in the IT-15 gene, also called the HD gene or HTT [12, 167, 168].
Generally speaking, people with over 36 CAG repeats in this gene may develop Huntington’s disease, and people with over 39 CAG repeats are likely to develop Huntington’s disease. The more repeats a person has, the earlier in life they develop the disease. Up to 120 CAG repeats have been observed in a single person’s genome .
In some people with Parkinson’s, the disease can be explained by mutations in one or more different genes. The names and functions of these genes are in bold below, and individual mutations (and SNPs) follow.
Parkinson’s disease has been associated with the genes :
- SNCA produces alpha-synuclein, a protein in brain cells that may be involved in dopamine release and transport. At least 30 different mutations in SNCA are associated with Parkinson’s disease. These include: A30P (rs104893878), E46K (rs104893875), H50Q (rs201106962), G51D (rs431905511) and A53T (rs104893877) .
- LRRK2 produces the leucine-rich repeat kinase 2, which helps transmit signals and turns on and off different cell functions. More than 100 different mutations in LRRK2 are associated with Parkinson’s disease. These include: G2019S (rs34637584), R1441C/G/H (rs33939927, rs33939927, rs34995376), Y1699C (rs35801418), and I2020T (rs35870237) [170, 171].
- PRKN produces parkin, which helps break down and dispose of damaged or unneeded proteins. More than 200 different PRKN mutations are associated with early-onset Parkinson’s disease, including V148E (rs1060502319) [172, 173].
- GBA produces glucosylceramidase beta, another part of the cell’s breakdown machinery. Many mutations at GBA are associated with Parkinson’s disease. These include: K480N (rs1057519356), P426L (rs1057519357), P427L (rs1057519357), and I407T (rs10575358).
- PINK1 produces PTEN-induced kinase 1, which may protect the mitochondria within cells from stress. Dozens of mutations at PINK1 may be associated with Parkinson’s disease. These include: P399L (rs119451946), H271Q (rs28940284), L347P (rs28940285), and Q456* (rs45539432) [174, 175].
- PARK7 produces a protein that protects neurons against stress and cell death. More than 25 mutations of this gene have been associated with Parkinson’s disease. These include: A39S (rs137853051), E163K (rs200968609), and L166P (rs38938172).
- VPS35 (also called PARK17) produces vacuolar protein sorting 35, which transports proteins within cells. The Asp620Asn mutation (rs188286943) of this gene has been strongly associated with adult-onset Parkinson’s disease [176, 177].
- EIF4G1 (also called PARK18) produces the eukaryotic translation initiation factor 4 gamma 1, which is important for making new proteins within cells. The R1205H (rs112176450) and A502V (rs111290936) mutations in this gene are linked to adult-onset Parkinson’s disease [178, 179].
- DNAJC13 (also called PARK21) produces the receptor-mediated endocytosis 8 protein, which helps transport compounds into cells. The N855S (rs387907571) mutation of this gene is associated with late-onset Parkinson’s disease [180, 181].
- CHCHD2 (also called PARK22) produces a protein that helps regulate cell death. Two rare mutations of this gene, T61I (rs864309650) and R145Q (rs752169833), have been associated with Parkinson’s disease [182, 183, 184].
Limitations and Caveats
Most if not all of the natural substances and pharmaceutical drugs listed in this article affect parts of the brain other than the basal ganglia. These effects should also be considered before they are supplemented or added to an existing regimen. Always consult your doctor before using supplements, especially if you are taking medication for mental illness or movement conditions.
Our knowledge of the human brain is still limited. Our understanding of the role of the basal ganglia in learning, the regulation pathways of these neurons, and the mechanisms of effect of various drugs continues to evolve. The recommendations and conclusions in this article are therefore subject to change.
The basal ganglia are sometimes called the reptilian brain, as scientists thought we inherited them from a lizard ancestor. In fact, they may go back to an even older evolutionary ancestor. Rooted deep within the brain, the basal ganglia orchestrate some of your most basic instincts and help control your balance and movement.
Your basal ganglia use two main neurotransmitters to communicate: GABA and dopamine. Imbalances or damage in the basal ganglia can affect the harmony of these important brain messengers, which can result in:
- Anxiety, depression, or other mental health problems
- Neurological diseases like Parkinson’s or Huntington’s
- ADHD, autism, or milder forms of problems with attention and socializing
And many others. Some safe lifestyle interventions and supplements may be able to correct milder imbalances. Ultimately, however, only a qualified neurologist can assess the function of your basal ganglia and brain.