Serotonin
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Objectives
~ Identify the functions of serotonin
~ Explore the connection between serotonin and depression and anxiety
~ Explore the relationship of serotonin to other neurotransmitters
~ Learn about causes of low serotonin
~ Identify interventions to naturally increase serotonin
Identify The Functions of Serotonin
~ Serotonin is among the many neurotransmitters that participate in the regulation of cortisol, prolactin and growth hormone secretion
~ Low dopamine low prolactin
~ Prolactin regulates behavior, the immune system, metabolism, reproductive systems
~ Prolactin decreases estrogen and testosterone
~ Prolactin is high during times of stress
Identify The Functions of Serotonin
~ Serotonin also appears to be involved in the regulation of circadian rhythms.
~ Melatonin is synthesized from serotonin
~ 5-HT and SSRIs have an inhibitory effect on feeding behavior.
~ Hypothalamus also receives signals from pleasure pathways that use dopamine, endocannabinoids and serotonin as messengers, which influence eating behavior and influence the release of ghrelin (hunger) or leptin (satiation)
Serotonin & Depression and Anxiety
~ 5HT1A, 5HT2A, 5HT2C, 5HT4,6,7 are all involved in the regulation of depression and anxiety
~ People with too much serotonin have anxiety symptoms.
~ Frick A, Åhs F, Engman J, et al. Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study. JAMA Psychiatry. 2015.
~ https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression
~ Patients with anxiety produced more serotonin in the amygdala https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2319711
~ People with too little serotonin may not feel depressed https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471964/
Causes of High Serotonin
~ Selective serotonin reuptake inhibitors (SSRIs)
~ Serotonin and norepinephrine reuptake inhibitors (SNRIs), antidepressants such as trazodone, duloxetine (Cymbalta) and venlafaxine (Effexor)
~ Bupropion (Wellbutrin, Zyban), an antidepressant and tobacco-addiction medication
~ Tricyclic antidepressants
~ Monoamine oxidase inhibitors (MAOIs)
~ Anti-migraine medications such as triptans (Axert, Amerge, Imitrex), carbamazepine (Tegretol) and valproic acid (Depakote)
~ Opioid pain medications
Causes of High Serotonin
~ Lithium (Lithobid), a mood stabilizer
~ Illicit drugs, including LSD, Ecstasy, cocaine and amphetamines
~ Herbal supplements, including St. John's wort, ginseng and nutmeg
~ Over-the-counter cough and cold medications containing dextromethorphan
~ Anti-nausea medications such as metoclopramide (Reglan), and ondansetron (Zofran)
~ Linezolid (Zyvox), an antibiotic
~ Ritonavir (Norvir), an anti-retroviral medication used to treat HIV/AIDS
Serotonin Syndrome–HARMFUL
~ Hyperthermia
~ Anticognitive
~ Reflexes
~ Myoclonus
~ Fast heart rate
~ Unconsciousness
~ Loss of GI control
Causes of Low Serotonin
~ High Cortisol
~ Pain/inflammation
~ Stress
~ Low estrogen
~ High testosterone
~ Poor diet (Tryptophan, Vitamins)
~ Insufficient vitamin D
5-HT1A
~ Memory(agonists ↓)
~ Learning (agonists ↓)
~ Anxiety (agonists ↓)
~ Depression (agonists ↓)
~ Positive, negative, and cognitive symptoms of schizophrenia (partial agonists ↓)
~ Analgesia (agonists ↑)
~ Aggression (agonists ↓)
~ Dopamine release in the prefrontal cortex (agonists ↑)
~ Serotonin release and synthesis (agonists ↓)
5-HT1A partial agonists
~ Antianxiety: Buspar
~ Antidepressant: Vilazodone/Viibryd
~ Atypical Antipsychotics
~ Clozapine/Clozaril
~ Ziprasidone/Geodon
~ Aripiprazole/Abilify
5-HT1B
~ Play a critical role in autoregulation of serotonergic neurotransmission, and are implicated in disorders of serotonergic function, particularly emotional regulation
~ Inhibits the release of dopamine
~ Inhibits the release of serotonin
~ Decreases glutamatergic transmission
~ Higher preference for alcohol (antagonist ↑)
~ OCD symptoms (agonists ↑)
~ Vasoconstriction (agonists ↑)
~ Aggression (agonists ↓)
5-HT1B
~ Agonists—Migraine Meds/vasoconstrictors
~ Ergotamine
~ Oxymetazoline
~ Sumatriptan
~ Zolmitriptan
~ Partial agonists
~ Dextromethorphan
~ Ziprasidone (Geodon)
~ Antagonists and inverse agonists
~ Methiothepin (antipsychotic)
~ Yohimbine (aphrodisiac)
~ Metergoline (dopamine agonist)
~ Aripiprazole (Abilify)
5-HT2A
~ Activation of the 5-HT2A receptor is necessary for the effects of the “classic” psychedelics like LSD, psilocin and mescaline
~ 5-HT2A receptor antagonists interfere with the heightened state of dopamine activity
~ Evidence implies that selective 5-HT2A antagonists may be considered useful in the treatment of psychosis, and possibly alcohol and cocaine dependence.
~ Activates monocytes and modulates cytokine and chemokine production in lipopolysaccharides
~ Wishing Away Inflammation? New Links between Serotonin and TNF Signaling Martin Pelletier and Richard M. Siegel (NIH)
5-HT2A
~ Full Agonist
~ Mexamine is a full agonist to several serotonin receptors.
~ Partial Agonist
~ Efavirenz, an antiretroviral drug, produces psychiatric side effects thought to be mediated by 5-HT2A.
~ Mefloquine, an antimalarial drug
~ Lisuride, an antiparkinson dopamine agonist/antagonist
~ Antagonist
~ Trazodone is a potent 5-HT2A antagonist, as well as an antagonist on other serotonin receptors.
~ Mirtazapine is a 5-HT2A, 5-HT2C, and 5-HT3 antagonist
~ Typical and Atypical antipsychotic
5-HT2b
~ The 5-HT2B receptor regulates cardiac structure and functions
~ 5-HT2B antagonists have previously been proposed as treatment for migraine headaches
~ More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease.
5-HT2b
~ Agonists
~ MDMA (Ecstasy)
~ LSD-25
~ Chlorphentermine (appetite suppressant)
~ Most SSRIs
~ Increased risk of valvulopathy
~ Antagonist
~ Aripiprazole (Abilify)
~ Amisulpride (Solian (antipsychotic))
5-HT2C
~ Studies indicate that 5-HT2C receptor activation will regulate appetite and food consumption (Lorcaserin) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047218/
~ A 5-HT2C agonist may be expected to reduce positive symptoms of schizophrenia by reducing dopamine release (aripiprazole/Abilify)
~ Dopamine release (agonists ↓)
~ Acetylcholine release in the prefrontal cortex (agonists ↑)
~ Antidepressant effects (agonists & antagonists ↑)
5-HT4
~ Located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system
~ Functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters
~ Movement of food across the GI tract (agonists ↑)
~ Memory & learning (agonists ↑)
~ Antidepressant effects (agonists ↑)
https://en.wikipedia.org/wiki/5-HT4_receptor
5-HT5A
~ Implicated in a wide range of psychiatric conditions
~ Has vasoconstrictive and vasodilatory effects
~ Memory consolidation.
~ Antagonist: Risperdone
~ Agonist: Valernic Acid (a component of valerian)
5-HT6
~ Plays a role in functions like motor control, emotionality, cognition, and memory
~ Antagonism of central 5HT6 receptors has been shown to
~ Increase glutamatergic and cholinergic neurotransmission
~ Facilitate dopamine and norepinephrine release in the frontal cortex
~ Antagonists: Atypical antipsychotics
5-HT6
~ Agonism
~ Enhances GABAergic signaling
~ Inhibits dopamine and norepinephrine release in the frontal cortex
~ 5-HT6 receptor agonists improve learning and memory in animal models
~ Can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer’s disease.
5-HT7
~ Involved in thermoregulation, circadian rhythm, learning, mood regulation and memory, and sleep
~ Models of anxiety and schizophrenia have yielded mixed results with no clear role for the 5-HT7 receptor described in these disorders.
~ Some data are available for epilepsy, migraine, and pain but it is still very early to draw any definitive conclusions.
~ There is a considerable amount of evidence supporting a role for the 5-HT7 receptor in depression
5-HT7
~ Agonist
~ Aripiprazole (Abilify)
~ Antagonist
~ Amitriptyline
~ Clozapine (Clozaril)
~ Lurasidone
~ Olanzapine (Zyprexa)
~ Ziprasidone (Geodon)
~ Risperidone (Inactivating)
Increase Serotonin
~ Exercise
~ Sunlight
~ Reduce Pain
~ Reduce Stress
~ Proper Nutrition
Interventions for High Serotonin
~ Lower estrogen
~ Increase GABA
Summary
~ Serotonin has a multitude of effects in the body
~ Serotonin is partially responsible for preventing leaky gut and associated inflammation
~ Low serotonin can lead to low levels of other hormones necessary for feelings of pleasure
~ High serotonin is implicated in anxiety based disorders
~ There is no clear clinical evidence that low serotonin CAUSES depression, but it may be involved in a the chain of events that leads to depression