Norepinephrine
The Get Up and Go Neurotransmitter
Instructor: Dr. Dawn-Elise Snipes PhD, LPC-MHSP, LMHC
Executive Director, AllCEUs Counselor Education
- CEUs are available for this presentation at https://allceus.com/member/cart/index/product/id/960/c/
- In Australia, the professional development course is located at https://australia.allceus.com/member/cart/index/product/id/960/c/
Objectives
~ What is it and what is it’s function?
~ How does it interact with serotonin, dopamine and GABA?
~ What are symptoms of excess?
~ How do you decrease it?
~ What are symptoms of insufficiency?
~ How do you increase it?
What is it
~ General function of norepinephrine is to mobilize the brain and body for action
~ Norepinephrine release is lowest during sleep, rises during wakefulness, and reaches much higher levels during situations of stress or danger
~ Norepinephrine functions mainly as a neurotransmitter with some function as a hormone (being released into the bloodstream from the adrenal glands)
~ NE affects the behaviors of individuals including a modulation of vigilance, arousal, attention, motivation, reward and also learning and memory
What is it
~ It enhances processing of sensory inputs, attention, and formation and retrieval of long-term and working memory
~ NE is involved in the clinical features of cerebral aging, cognitive slowing, and loss of behavioral adjustment
~ Both NE and 5-HT activity is lower in bipolar disorder
~ Neither 5-HT nor NE depletion induced clinical depression in healthy subjects or worsened depression in unmedicated symptomatic patients with major depression.
~ This finding suggests that the cause of depression is more complex than just an alteration in the levels of 5-HT and/or NE, and may be more directly caused by dysfunction in brain areas or neuronal systems modulated by neurotransmitters.
What is it
~ Like SSRIs, SNRIs are thought to work by promoting neuroplasticity in the brain.
~ Higher levels of norepinephrine and serotonin may stimulate neurons to remodel themselves and their circuits in a variety of ways that promote increased flexibility.
~ NE plays a determinant role in executive functioning regulating cognition, motivation, and intellect, which are fundamental in social relationships.
~ Social dysfunction is possibly one of the most important factors affecting the quality of life in depressed patients
What is it
~ Phenylalanine->Tyrosine->L-dopa->Dopamine->Epinephrine->Norepinephrine
~ Norepinephrine is synthesized from dopamine (tyrosine) amino acid found in proteins such as meat, nuts, and eggs. Dairy products such as cheese also contain high amounts of tyrosine (the amino acid is named for “tyros,” the Greek word for cheese).
~ Modulates immune response. Suppress neuroinflammation when released in the brain.
~ Up to 70% of norepinephrine projecting cells are lost in Alzheimer’s Disease
~ Increase the force of skeletal muscle contraction and the rate and force of contraction of the heart.
~ Increase heart rate, blood pressure, and levels of glucose and fat in the blood
What is it
~ In the eyes, an increase in production of tears, making the eyes moister, and pupil dilation.
~ In brown adipose tissue, an increase in calories burned to generate body heat.
~ In the kidneys, a release of renin and retention of sodium in the bloodstream.
~ In the liver, an increase in production of glucose
~ In skeletal muscles, an increase in glucose uptake.
~ In fat cells, an increase in fat burning.
~ In the stomach and intestines, a reduction in digestive activity and decreases in gastrointestinal mobility
Norepinephrine Deficiency & Prolonged Stress
~ In the early stages of prolonged or severe stress, the stress response system is overactive and norepinephrine and other adrenal stress hormone levels are typically elevated.
~ This increases arousal, amplifies the emotional reaction to stress, and can manifest as insomnia, anxiety, depression, irritability, or emotional instability.
~ But prolonged stress leads to underactivity of the stress response system, resulting in norepinephrine deficiency, along with cortisol and epinephrine depletion. (Hypocortisolism)
~ This lowers arousal and can result in low energy, daytime fatigue, concentration/focus issues, and general apathy.
Symptoms of Insufficiency
~ ADHD
~ Parkinson’s disease and diabetes cause degeneration of norepinephrine neurons leading to bradycardia and hypotension
~ Low levels of epinephrine and norepinephrine can contribute to a variety of physical and mental conditions, including:
~ Depression
~ Fibromyalgia
~ Hypoglycemia
~ Migraine headaches
~ Restless leg syndrome
~ Sleep disorders
Increase Norepinephrine
~ Cocaine
~ Tricyclic antidepressants
~ Amphetamines
~ Steroids
~ Psychostimulants (ADHD medications) increase dopamine and norepinephrine
Increase Norepinephrine
~ Exercise
~ Stress
~ Phenylalanine (precursor)
~ Tyrosine (precursor)
~ Carnitine
~ Levels of dopamine, norepinephrine, and serotonin all increase with nicotine usage
Symptoms of Excess
~ Aches and pains
~ Rapid heartbeat
~ Elevated blood pressure
~ High blood pressure
~ Anxiety
~ Excessive sweating
~ Heart palpitations
~ Headaches
Drugs that Increase Norepinephrine
~ Norepinephrine reuptake inhibitors (NRIs) sed to treat major depressive disorder (MDD), anxiety, panic disorder, narcolepsy, and ADHD (Strattera (atomoxetine))
~ Norepinephrine-dopamine reuptake inhibitors (NDRIs) used for clinical depression, ADHD, and narcolepsy. Focalin (dexmethylphenidate), Wellbutrin (bupropion)
~ Selective serotonin reuptake inhibitors (SSRIs) used to treat MDD and anxiety disorders. Zoloft (sertraline)
Drugs that Increase Norepinephrine
~ Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be used to treat bipolar depression**, MDD, ADHD, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), chronic nerve pain, and fibromyalgia. Cymbalta (duloxetine), Savella (milnacipran)–Fibro
~ Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs) developed to treat depression but can also be used to treat ADHD, chronic pain, and obesity. (Effexor (venlafaxine), Serzone (nefazodone))
Reducing Norepinephrine
~ Beta blockers are frequently used to treat glaucoma, migraine, and a range of cardiovascular problems.
~ Alpha blockers are used to treat cardiovascular conditions, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder.
~ They may, however, have significant side-effects, including a drop in blood pressure.
Reducing Norepinephrine
~ Alpha-2 agonists often have a sedating effect, and are commonly used in treatment of drug or alcohol dependence.
~ Because alpha-2 receptors are inhibitory net effect of agonists is usually to reduce the amount of norepinephrine released (Clonidine)
~ Many important psychiatric drugs exert strong effects on noradrenaline systems in the brain, resulting in side-effects that may be helpful or harmful: Amphetamines, psychostimulants, MAOIs, NDRIs, SNRIs
Neurotransmitters and Mood
~ Norepinephrine improves cognition, memory and energy levels
~ Dopamine improves motivation, attention, energy and reward responses
~ Serotonin helps us regulate our emotions
~ When participants were given an SSRI
~ The amygdala became less active. This indicates that our brains become less emotionally reactive after a single dose of an antidepressant.
~ There is increased activity in frontal regions of the brain, including a region of the prefrontal cortex involved in regulating emotions, suggesting that SSRIs may increase capacity to regulate our emotions. https://www.sciencedirect.com/science/article/pii/S0149763413001814
Summary
~ Norepinephrine is synthesized from dopamine
~ Tyrosine deficiency
~ Antipsychotics
~ Norepinephrine is one of the main fight or flight chemicals
~ Prolonged stress leads to norepinephrine reduction
~ Norepinephrine is involved in depression and Alzheimer’s, migraines, RLS and fibromyalgia
~ Too much norepinephrine can lead to symptoms of anxiety and panic. Parkinsons, RLS, ADHD, depression