245 – Neurobiology Understanding the Big 6 Neurotransmitters
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Neurobiology: Dopamine, GABA, Serotonin, Acetylcholine
Dr. Dawn-Elise Snipes PhD, LPC-MHSP, LMHC, CCDC
Executive Director, AllCEUs.com
Podcast Host: Counselor Toolbox and Happiness Isn’t Brain Surgery
Objectives
~ Define Neurobiology
~ For the following neurotransmitters, Dopamine, GABA, Serotonin, Acetylcholine, identify
~ Their mechanism of action/purpose
~ Where they are found
~ Symptoms of excess & insufficiency
~ Nutritional building blocks
~ Medications
What is Neurobiology
~ Neurobiology is the study of the brain and nervous system which generate sensation, perception, movement, learning, emotion, and many of the functions that make us human
Think about
~ A client who presents with apathy/loss of pleasure, sleep disturbances, fatigue, and difficulty concentrating
~ What would your diagnosis be?
~ What medication would you expect the doctor to put him on?
Dopamine
~ Mechanism of action/purpose
~ movement
~ memory
~ pleasurable reward
~ behavior and cognition
~ attention
~ inhibition of prolactin production
~ sleep
~ mood
~ learning
Dopamine
~ Mechanism of action/purpose
~ Altered dopamine neurotransmission is implicated in:
~ Cognitive control (racing thoughts)
~ Attentional control
~ Impulse control
~ Working memory
~ Mood
~ Motivation
~ Sleep
Dopamine
~ Where is it found
~ Precursor, L-DOPA is synthesized in brain and kidneys
~ Dopamine functions in several parts of the peripheral nervous system
~ In blood vessels, it inhibits norepinephrine release and acts as a vasodilator (relaxation)
~ In the kidneys, it increases sodium and urine excretion
~ In the pancreas, it reduces insulin production
~ In the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa
~ In the immune system, it reduces lymphocyte activity.
~ The dopaminergic system in autoimmune diseases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968755/
Dopamine
~ Symptoms of excess & insufficiency
~ Excess of dopamine
~ Unnecessary movements, repetitive tics
~ Psychosis
~ Hypersexuality
~ Nausea
~ Most antipsychotic drugs are dopamine antagonists
~ Dopamine antagonist drugs are also some of the most effective anti-nausea agents
Dopamine
~ Symptoms of excess & insufficiency
~ Insufficient dopamine
~ blunting of affect/apathy
~ Loss of motivation
~ Pain
~ Parkinson’s Disease
~ Restless legs syndrome
~ Attention deficit hyperactivity disorder (ADHD)
~ Neurological symptoms that increase in frequency with age, such as decreased arm swing and increased rigidity.
~ Changes in dopamine levels may also cause age-related changes in cognitive flexibility.
Dopamine
~ Symptoms of excess & insufficiency
~ Insufficient dopamine
~ Lack of motivation
~ Fatigue
~ Apathy, Inability to feel pleasure
~ Procrastination
~ Low libido
~ Sleep problems
~ Mood swings
~ Hopelessness
~ Memory loss
~ Inability to concentrate
Dopamine
~ Nutritional building blocks
~ Eating a diet high in magnesium and tyrosine rich foods will ensure you’ve got the basic building blocks needed for dopamine production.
~ Here’s a list of foods known to increase dopamine:

Dopamine
~ Medications
~ Dopamine in blood is unable to cross the blood-brain barrier to reach the brain.
~ Most common dopamine AGONISTs (Parkinson’s, Restless Legs, negative symptoms)
~ Mirapex & Requip
~ Levodopa-Carbidopa combination is actually converted to dopamine in the brain
~ Buspirone

Dopamine
~ Medications
~ Most common dopamine antagonists (positive symptoms)
~ Risperdone, Haldol, Zyprexa
~ Metoclopramide (Reglan) is an antiemetic
Dopamine
~ Supplements which May Increase Dopamine
~ L-theanine is an amino acid uniquely found in green tea that creates an alert state of relaxation without drowsiness.
~ Rhodiola rosea, or “golden root,”
~ Improving depression, enhancing work performance, eliminating fatigue and treating symptoms resulting from intense physical and psychological stress.
~ Enhancing the stability of dopamine and supporting its reuptake. This leads to notable decreases in depression, anxiety, and fatigue, as well as an increased ability to handle stress
~ https://universityhealthnews.com/daily/depression/dopamine-supplements-for-improving-mood-and-motivation/

Dopamine
~ Blood levels of antipsychotic medications and lithium are especially sensitive to hydration levels
~ NMS
~ Caused by a sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agents or from blockade of dopamine receptors.
~ Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate.
~ Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.
Dopamine: Age Related Changes
~ Dopamine levels decline by around 10% per decade from early adulthood and have been associated with declines in cognitive and motor performance
~ Dopamine levels are also impacted by availability of estrogen
Norepinepherine
~ Function
~ Fight or flight excitatory neurotransmitter
~ Implicated in motivation
~ Symptoms of Insufficiency
~ When faced with severe stress, the stress response system activates raising norepinephrine and stress hormones
~ This increases arousal, increases insomnia, anxiety, depression, irritability, or emotional instability.
~ Prolonged stress leads to underactivity of the stress response system (desensitization)
~ This lowers arousal and can result in low energy, daytime fatigue, concentration/focus issues, and general apathy.
Psychiatry Clin Neurosci. 2014 Jan;68(1):1-20.
Norepinepherine
~ Symptoms of Excess
~ ADHD or problems with concentration
~ Depression
~ Anxiety
~ Poor Sleep
Arch Gen Psychiatry. 1988 Sep;45(9):849-57.
J Psychosom Res. 2004 Oct;57(4):353-8.

Norepinepherine
~ Nutrition
~ Tyrosine rich foods
~ bananas
~ beans and legumes
~ chicken
~ cheese
~ chocolate
~ eggs
~ fish and seafood
~ meat
~ oatmeal
~ A daytime nap can also double your levels of norepinephrine

Glutamate
~ Is an amino acid (present in most high protein foods)
~ Most prevalent excitatory neurotransmitter
~ Used to make GABA (teeter-totter)
~ Facilitates learning and memory
~ Excess glutamate is associated with
~ Panic attacks / anxiety
~ Impulsivity
~ OCD
~ Depression

Glutamate
~ Availability declines with age
~ Affected by serotonin availability
~ Insufficient
~ Agitation
~ Memory loss
~ Sleeplessness
~ Low energy level
~ Depression
GABA
~ Mechanism of action/purpose
~ Anti-anxiety, Anti-convulsant
~ GABA is made from glutamate
~ GABA functions as an inhibitory neurotransmitter
~ GABA does the opposite and tells the adjoining cells not to “fire”
~ Where is it found
~ Close to 40% of the synapses in the human brain work with GABA and therefore have GABA receptors.

GABA
~ Symptoms of insufficiency
~ Anxiety
~ Depression
~ Difficulty concentrating
~ Insomnia
~ Seizure disorders

~ Symptoms of excess
~ Excess sleepiness
~ Shallow breathing
~ Decreased blood pressure
~ Memory problems
~ Dizziness
~ Blurred vision
~ Slurred speech
~ Weakness

GABA
~ Nutritional building blocks
~ Fermented foods sauerkraut, yogurt
~ Almonds & walnuts
~ Cherry tomatoes
~ Banana
~ Brown rice
~ Potato
~ Oats
~ Lentils
~ Vitamin B6, if deficient, may impair the production of GABA as it is a cofactor nutrient.
GABA
~ Nutritional building blocks
~ Inositol (Vitamin B-8)
~ Wheat germ
~ Brown rice
~ Green leafy vegetables
~ Nuts
~ Navy and Lima beans
GABA
~ Medications
~ Drugs that increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effect
~ Gabapentin (neurontin) is a GABA analogue used to treat epilepsy and neurotic pain.
~ Benzodiazepines and Barbiturates including GHB, Valium, Xanax
~ Baclofen (muscle relaxant)
~ Klonapin

Serotonin
~ Mechanism of action/purpose
~ Helps regulate
~ Mood
~ Sleep patterns
~ Appetite
~ Pain
Serotonin
~ Where is it found
~ Brain
~ Gut/Intestines
Serotonin
~ Symptoms of excess (Serotonin Syndrome)
~ Shivering
~ Diarrhea
~ Muscle rigidity
~ Fever
~ Seizures
~ Irregular heartbeat
~ Agitation
~ High blood pressure

Serotonin
~ Insufficiency
~ Depression
~ Anxiety
~ Pain sensitivity
~ Poor sleep
~ Difficulty concentrating
~ Carb cravings
~ Constipation

Serotonin
~ Nutritional building blocks
~ Foods rich in tryptophan, an amino acid that converts to serotonin in the brain.
~ Whole-wheat
~ Potatoes
~ Brown rice
~ Lentils
~ Oats
~ Beans
Serotonin
~ Medications & Supplements
~ SSRIs
~ SNRIs
~ 5-HTP
~ SAM-e
~ St. Johns Wort
~ Atypical Antipsychotics

Understanding SOME of the Serotonin Receptors
Ways Serotonin is Increased
~ Increase in serotonin synthesis
~ L-Tryptophan (esp. supplementation)
~ Reduction in serotonin breakdown
~ MAOIs: Isocarboxazid (Marplan) and phenelzine (Nardil)
~ Increase serotonin release
~ Amphetamines (ADHD medication, MDMA)
~ Anorectics (appetite suppressants (dexadrine))
~ Anti-migraine medications such as triptans (Axert, Amerge, Imitrex), carbamazepine (Tegretol) and valproic acid (Depakene)
Ways Serotonin is Increased
~ Stimulation of Post Synaptic Receptors
~ Buspirone
~ https://www.ncbi.nlm.nih.gov/pubmed/9826102
~ Lithium
~ Pain medications such as opioid pain medications including codeine (Tylenol with codeine), fentanyl (Duragesic), hydrocodone meperidine (Demerol), oxycodone (Oxycontin, Percocet, Percodan) and tramadol (Ultram).

Ways Serotonin is Increased
~ Serotonin Reuptake Inhibitor
~ SSRI Antidepressants (Paxil, Prozax, Zoloft)
~ Ultram (SSRI + mu-receptor activation)
~ Trazadone (SARI: Serotonin Agonist and Reuptake Inhibitor)
~ Tricyclic Antidepressants (i.e. Elavil (amitriptyline), Tofranil (imipramine), and Pamelor (nortriptyline ))
~ Serotonin and norepinephrine reuptake inhibitors (SNRIs), antidepressants such as duloxetine (Cymbalta) and venlafaxine (Effexor)
~ Bupropion (Wellbutrin, Zyban) antidepressant and tobacco-addiction medication. Norepinephrine-dopamine reuptake inhibitor (NDRI)

Other Drugs That Act To Raise Serotonin
~ Illicit drugs, including LSD, Ecstasy, cocaine and amphetamines
~ Herbal supplements, including St. John's wort, ginseng and nutmeg, 5-HTP
~ Over-the-counter cough and cold medications containing dextromethorphan (Delsym, Mucinex DM, others)
~ Anti-nausea medications such as granisetron, metoclopramide (Reglan), droperidol (Inapsine) and ondansetron (Zofran)
~ Linezolid (Zyvox), an antibiotic
~ Ritonavir (Norvir), an anti-retroviral medication used to treat HIV/AIDS

http://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/dxc-20305673
CAN Identify
~ C = Cognitive changes including agitation, confusion, euphoria, insomnia, hypomania and hallucinations
~ A= Autonomic changes including tachycardia, fever, arrhythmias, sweating, dilated pupils
~ N= Neuromuscular changes including tremor, rigidity, incoordination, seizures

Serotonin Age Related Changes
~ Serotonin goes down when estrogen or testosterone go down (Dr. Jacques Lorrain. (1994) Comprehensive Management of Menopause)
~ Melatonin doesn’t decline as we age, unless serotonin declines significantly
Acetylcholine
~ Mechanism of action/purpose
~ In lower amounts, ACh can act like a stimulant by releasing norepinephrine (NE) and dopamine (DA).
~ Memory
~ Motivation
~ Higher-order thought processes
~ Sexual desire and activity
~ Sleep
Acetylcholine
~ Symptoms of excess
~ Depression (all symptoms)
~ Nightmares
~ Mental Fatigue
~ Anxiety
~ Inverse relationship between serotonin and acetylcholine

Acetylcholine
~ Insufficiency
~ Alzheimers/dementia
~ Parkinsons
~ Impaired cognition, attention, and arousal
~ Cholinergic and GABAergic pathways are intimately connected in the hippocampus and basal forebrain complex.
Acetylcholine
~ Nutritional building blocks
~ Foods high in choline
~ Meats
~ Dairy
~ Poultry
~ Chocolate
~ Peanut butter
~ Wheat germ
~ Brussels sprouts and broccoli
Acetylcholine
~ Medications
~ Cholinergics (Increase)
~ Used for glaucoma, bladder control and severe muscle weakness
~ Anticholinergics
~ May worsen GERD
~ Used for extrapyrimadal symptoms is treating schizophrenia
~ Muscular spasms
~ Akathisia: A feeling of internal motor restlessness, tension, nervousness, or anxiety[
~ Drug-induced parkinsonism
~ Tardive dyskinesia: involuntary muscle movements in the lower face and distal extremities

Acetylcholine
~ Medications
~ Anticholinergics
~ Atropine
~ Benzatropine (Cogentin)
~ Chlorpheniramine (Chlor-Trimeton)
~ Dimenhydrinate (Dramamine)
~ Diphenhydramine (Benadryl, Sominex, Advil PM, Unisom)
~ Hydroxyzine (Atarax, Vistaril)
~ Bupropion (Zyban, Wellbutrin)
~ Dextromethorphan – Cough suppressant
Acetylcholine
~ Anticholinergic drugs are used to treat a variety of conditions:
~ Gastrointestinal disorders (e.g., gastritis, diarrhea, diverticulitis, ulcerative colitis, nausea, and vomiting)
~ Genitourinary disorders (e.g., cystitis, urethritis, prostatitis)
~ Respiratory disorders (e.g., asthma, chronic bronchitis, and chronic obstructive pulmonary disease [COPD])
~ Insomnia, although usually only on a short-term basis.

Summary
~ There are a variety of different neurotransmitters involved in addiction and mental health disorders
~ It is not always about increasing a neurotransmitter. Sometimes you need to decrease it.
~ Human brains try to maintain homeostasis and too much or too little can be bad
~ A balanced diet will provide the brain the necessary nutrients in synergystic combinations
Think about
~ A client who presents with apathy/loss of pleasure, sleep disturbances, fatigue, and difficulty concentrating

References
~ Res Nurs Health. 2014 Jun;37(3):185-93. doi: 10.1002/nur.21595. Epub 2014 Apr 3. Neurobehavioral effects of aspartame consumption.Lindseth GN1, Coolahan SE, Petros TV, Lindseth PD.
~ http://www.smithsonianmag.com/science-nature/could-diet-soda-cause-clinical-depression-586801/?no-ist
~ Understanding our Bodies: Dopamine and Its Rewards http://nutritionwonderland.com/2009/07/understanding-our-bodies-dopamine-rewards/
~ http://nutritionwonderland.com/2009/06/understanding-bodies-serotonin-connection-between-food-and-mood/

References
~ Myo-inositol content of common foods: development of a high-myo-inositol diet. http://ajcn.nutrition.org/content/33/9/1954.abstract
~ Neuroscience. 2002;111(2):231-9. GABA mechanisms and sleep. Gottesmann C.
~ Biofactors. 2006;26(3):201-8. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Abdou AM1, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H.

References
~ Neuropsychopharmacology: The Fifth Generation of Progress Editors: Kenneth L. Davis et. Al. Publisher Lippincott, Williams, & Wilkins, Philadelphia, Pennsylvania, 2002 http://www.acnp.org/publications/neuro5thgeneration.aspx

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