Lecture 11 - Serotonin Flashcards
How does LH act as a model for depression
•Serotonin is up-regulated in the Hippocampus during LH
•it kind of works as a model for depression, e.g. being subdued
- it’s an unavoidable stress cause of depression
•Issues with it:
X - but cant compare this to humans
X - exhaustive depression doesnt happen to all animals, and even if it does, they only stay like this for 1-2 ays
- animals often get over this, but it depends on the environment
What does gut motility mean in this sense?
Gut motility is like your digestive muscles and stuff like that, like swallowing and contracting muscles to process food through tubes and stuff
Outline serotonin and the gut
Around 90% of serotonin is in your gut neurons
- associated with motility and appetite
- Some anti-depressants are used to treat irritable bowel syndrome, where there is increased bowel motility
- IBS oten get gas, constipation, diarrhea - and anti-anxiety/ anti-depressants can help with this
Why do anti-depressants help with IBS?
- In IBS, gut is highly sensitive to the effects of stress, if you are in fight mode, you turn off your digestion - energy goes to heart and lungs, so you dont need to worry about eating
- If you are stressed for a long period of time, gut system becomes a bit dodgy
- Cortisol acting on gut systems trying to slow it down = reactive increase in motility
Outline serotonin in the raphe nucleus
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In CNS, serotonin is known as 5-HT
- 5-HT neurons are found in 7-8 Nuclei, called the Raphe Nuclei
- it is a red nuclei that sits in the brain stem, makes up part of the reticular formation
- Associated with the regulation of sleep/wake cycle (Circadian rhythm) - depression involves issues with sleep regulation
- Caudal (towards tail) Raphe Nuclei
- projects into cerebellum and spinal cord - suppression of pain pereception
- associated with bodys own pain killers (enkephalins and endorphines - Rostral (towards head) Raphe Nuclei
- Projects into entire CNS
- important for mood, cognition, memory
How is serotonin and the raphe nuclei involved in sleep
VIA THE SUPRACHIASMATIC NUCLEI (SCN)
- The raphe nuclei and SCN are reciprocally connected
1. SCN input to raphe nuclei alters 5-HT levels for sleep/ wake states
- Raphe Nuclei feeds back to SCN depending on vigiliance/ alertness
- produces serotonin
- part of reticular formation: Critical for regulating sleep and alertness
This reciprocal feedback provides adaptable yet stable basis for circadian rhythms
What is the SCN
The Suprachiasmatic Nucleus (SCN)
- Located just above optic chiasm
- received direct input fromr etina to allow external light to drive circadian rhythms
- this produces melatonin, which makes you sleepy
How is this system involved in SAD
Serotonin is inolved in Seasonal Affective Disorder
- so you can use lights to regulate circadian rhythms
How is 5-HT associated with mood
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- 5-HT probably just alters mood intensity (rather than mood states directly)
- Lisa Feldman Barret - intensities vs type of mood
- its likely 5-HT just alters intensity, not what emotion is felt
- cant give an epinephrine shot and they will become happy/ angry - depends on environment - Used to treat depression
- Sleep and depression closely related - 5-HT involved here
- SAD - 5-HT involved here too (SCN & Raphe)
- Linked to Generalised Anxiety Disorder
- and some phobias
Outline Generalised Anxiety Disorder
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Excessive worry that interefers with activities of daily life
- for more than 6 months
Rumination, agitation, over arousal about more than one topic, it keeps you awake at night
Not easy to treat, as it’s hard to stope people ruminating, trying to tell them not to think about this makes them think about it
- need to teach them about thought stopping
How do resources and social status interact with Serotonin
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Serotonin levels are higher with increased resources and better social status (complex form of a resource)
- Better social status (e.g. in monkeys), means you have better access to resources (e.g. food) = higher serotonin
- You are happier when you are higher status
- C Elegans
- very basic animals
- if you give them food, serotonin goes up - Lobsters
- Injected with serotonin = dominant, aggressive
- can be reversed by serotonin antagonists - Crayfish
- Social experience (status) alters responses to serotonin for fight-flight response in Crayfish
- fight or flight involved in social status, and this in turn influences serotonin
Outline serotonin in moneys and neglected monkeys and stuff
- Neglected/ Abused rhesus monkeys = lower 5-HT
- quite neurotic babies, dont tend to live very long (impulsive and risk taking), get into social trouble (abused by others)
- grow up to themselves become abusive parents
- might be related to learned behaviour
- but also perhaps due to low serotonin - Nice adoptive mums
- babies Become very sensitive to social structures
- if they get a super mum who is very nurturing and reassuring, their offspring becomed sensitised to social structures and can climb up the ladder very high
- but its not due to aggression, its because they are sensitive to social engagement, learning from their mums, so they can use other animals to create social structure - v good at working with others to get higher up in the structure
- If you are born with low serotonin, you should go down the route of aggression, but then getting a super adoptive mum, this can be reversed
What are the findings of nurture and nature and baby monkeys
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- In Macaques a pattern of low 5-HT and high stress (high levels of cortisol) = key predictor of aggresion, and maternal style when they group
- this in turns affects 5-HT in offspring, and their behaviour - Interactions between genetic polymorphisms in 5-HT metabolism (nurture) and rearing style (nurture) on behaviour & Cognitive function:
- if you give them a super mum (usually adoptive) they can overcome this and become smart/ sensitive to social interactions
What are the 2 categories of serotonin related drug s
- Aspecific - focus more on overall levels, compared to specific receptor subtypes
- not very specific to receptor subtypes
- most are aspecific - Receptor- Specific
Outline Aspecific serotonin related drugs
They just change overall levels of 5-HT, mostly not specific to receptor subtypes
- Incudes many recreational drugs, but these usually affect other monamine levels, like the catecholamines (DA, NE)
Side effects:
- due to appetite & Gut stuff: can put on weight
- interacts with hormone levels, impacting your libido, potentially quite a lot - so it can affect your relationships, how you view yourself etc
Therefore, to counter act this, researchers have tried to find receptor-specific drugs
Outline Receptor-Specific serotonin related drugs
Outline Aspecific serotonin related drugs
Can either be full or partial:
- Agnosists - help the effect of 5-HT
vs - Antagonists - block the effect of 5-HT
- Can either be fully, or partially
- So if level is low, can act as a helper, as an agonist
- but if level is too high, they then act as an antagonists - reduces it down, but still higher than the level it would be normally
- prevent it from being too low, but also from being too high
- Keeps it at a balnced level, but still more than enough
- They block the receptor
- not always the most effective, and if levels are low, still give some effect
- these Target 1 or more receptor, with varying affinities
How do drugs affect 5-HT
Several methods:
- BY AFFECTING BIOSYNTHESIS
- e.g. Tryptophan is a precursos for Serotonin
- but depends on levels of other amino acids at BB - Changing 5-HT clearance (reuptake) at pre-synpatic neuron
- Affecting its breakdown (MAO) in the cell
Outline Biosynthesis - tryptophan**
- method 1 of effecting 5-HT in the brain
- Tryptophan is an essential amino acid - found in bananas, salmon, dates, herring
- Doesnt immediately effect the brain, it depends on the BBB
- There is a Tryptophan Blood Brain transporter that transports it across the barrier, but it is also used by other amino acids, so might be busy
The rate limiting step is step 2
- Convering Tryptophan to 5-HTP (5-Hydroxy-L-Tryptophan) by TPH (Tryptophan Hyrdroxylase)
1. L-Tryptophan via TPH 2. 5-Hyrdroxy-L-Tryptophan (5-HTP) 3. Serotonin 4. 5-Hydroxyindoleacetic acid (5-HIAA)
What have findings about Tryptophan transporter found?
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- Mood induction experiments - using Branched-Chain Amino acids (BCAA) - block tryptophan blood-brain transporter
- this reduces 5-HT and induces depression
- not all the time - Receipine?***
- reduces all amino acids and can induce depression
- not in all people, not everyone is at risk of these effects