Lecture 10 - Norepinephrine, 5-HT and epinephrine and emotions Flashcards
Outline what Monamine’s are
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The collective term for these very important Neurotransmitters in your brain, they include: •Serotonin (5-HT) •Melatonin (sleeping) • Dopamine •Noradrenaline •Norepinephrine •Adrenaline •Epinephrine
What are the 2 subcategories of Monamines
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- Tryptamines
•Serotonin (5-HT)
•Melatonin (sleeping and can be used as an NT)
2. Catecholamines •Dopamine •Noradrenaline •Norepinephrine •Adrenaline •Epinephrine
Which ones are in the periphery
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1.
Epinephrine = In the brain
Adrenaline = Periphery
- Norepinephrine = in the brain
Noradrenaline = periphery
What are the precursors for Monamines
Amino acids:
•Phenylalanine -> tyrosine -> catecholamines
- including dopamine -> norepinephrine
- L-Tyrosine-> L-dopa-> Dopamine -> NE
•Tryptophan -> Serotonin
- present in bananas and herring
•Thyroid Hormones - can regulate 5-HT, NE and GABA at the level of synapses in this brain
Outline Phenylalanine as a precursor to catecholamines
•Phenylalanine (an amino acid) is a precursor to tyrosine
•Tyrosine is a precursor to catecholamines
- i.e. l-tyrosine to l-dopa
• L-tyrosine is metabolised into L-dopa, which is metabolised into NE
Outline Tyrptophan as a precursor to serotonin
•Tryptophan (an amino acid) is a precursor to serotonin
- competes with other amino acids at the brain blood barrier
- whether or not it goes up depends on what else is at the barrier
- lots of foods contain tryptophan, i.e. bananas - but its not as easy as just eating tryptophan to increase serotonin, although they will increase serotonin if they go through, they may not go through, it depends on what else is there
Outline the Dopamine metabolising pathways
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- Phenylalanine, is a precursor to:
- Tyrosine
- DOPA
- Dopamine
- Norepinephrine
- Epinephrine
Whats the unclear debate about NT’s and mental health
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It is unclear, whether:
- Neurotransmitters influence mental health
or
- Mental health, via behaviour, influences neurotransmitter levels
•E.g. not being active, laying in bed all day might influence NT levels
Outline Seligman & Maier (1967) - Learned Helplessness
Seligman & Maier (1967) - Learned Helplessness
- Looked at if you can condition an animal to be helpless
- Dogs were in a box, with a metal floor, there was a small barrier seperating out two sides
- Side A was electroctuted after a tone was played but the dog could just jump over to the other side, to side B
- BUT, if the dog was initially put in the box where there was just the wall was too high to jump over, maybe eve just a wall. when you then subsequently lowered that barrier, they still didnt make an attempt to jump over and escape
- they were conditioned to expect the tone, and then conditioned to just wait and take it - had learned to be helpless
Outline Seligman’s 3 dogs in a harness study
There were 3 dogs, two in a pair, and one control
Dog a: Control, received no shock Dog b (1st of the pair) This dog got a shock but could stop this shock by putting a paw on a lever Dog c (2nd of the pair) This dog got the same shocks as those in group, but couldn't stop it with their paws
Dog b was: erratic, unavoidable, un-escapable
Dog c was: meek, subdued and depressed, and when placed in the box, did nothing to escape
- Showed helplessness can be learned - you can teach people/ animals to be helpless
Outline Peterson, Maier & Seligman (1993) - learned helplessness
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They argued there were 3 levels to this learned helplessness:
- Emotional
- you feel helpless, emotional disruption - Motivational
- become passive and introverted - Cognitive
- tell yourself i cannt escape this
This might be a model of chronic stress, not a model of depression
Whats a limitation of generalising this to humans
X - learned helplessness doesnt always happen in all humans or all animals, you cant generalise it to everyone
X- doesnt happen in every animal/ every person
X - even in animals, it only stays up to 24-48 hours
- even in animals it doesnt last forever, eventually they will escape when they can
X - Revised this into explanatory style
Outline Explanatory style
- Explanatory style is how a human or an animal attributes what happens to them
- How we interpret and attribute stressful events
Those who attribute stressors as:
- internal (their fault)
- Stable
- Global (all situations)
- these humans tend to be more depressed
- negative explanatory style
Those who attribute stressors as
- external - this wasnt my fault
- Unstable - this is very unlikely to happen again
- Not global - This wont happen in any other situations
- these are less likely to develop learned helplessness
- also more likely to be a bit delusional, selectively remembering certain things, only select the positive stuff
Explanatory style is Linked to CBT
What did Weiner (1986) say depression was?
Depression is how we attribute causalities of certain events
- as internal, stable and global
Outline Petty (1994) - Norepinephrine and rats and learned helplessness ???????
Looked at Norepenephrine in the Hippocampus of rats
- in rats with inescapable stress, NE output in the Hippocampus actually increased
- rats were put in a situation of permanant inescapable stress
- NE didn’t go down like what was expected, it actually went up, hippocampus became very sensitive to stress (hypersensitivity)
Outline PTSD and coping with stress
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Learned Helplessness might actually be a model of something like PTSD, when you are in constant state of vigiliance/ stress
PTSD = response to uncontrollable traumatic stress leading to instructions, arousal (hypervigiliance) and avoidance (pink bear phenomenon)
- PTSD involves poor coping in mild stress, hypersensitivity to even slight stressors
- To qualify as PTSD, it has to be something that is life threatening, something that seriously endagegered the integrity of yourself - or seeing someone in a situation like this (if its a milder situation, it might just be panic disorder)
- After the event, you try to avoid thinking about it and being in situations that bring up this image - but if you try not to think about it, you will think about it
- if its constantly popping into your head, you become aroused, hypersensitive, insomnia perhaps (nightmares), become very vigilant
- being in this state, makes NE increases all the time, making the hippocampus over sensitive to stress
What was the initial idea about learned helplessness, and what is it now?
Initial idea: Learned helplessness causes NE and ST to go down
- because you cant do anything, you just sit there and take the punishment
Current idea: Whats actually been found is that if you have recurrent stress, NE and ST actually go up, because you are in a state of always being alert
- exhaustion of hyper vigiliance that makes these NT’s go up
- brain is actually working very hard and doing lots of stuff, producing lots of stuff
What did Hammack (2012) find about serotonin in the brain
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They found that also serotonin output also increases during learned helplessness and conditioned defeat (constantly thwarted when trying for a goal directed behaviour)
- output increases in Dorsal Raphe nuclues (main producer of 5-HT)
- other areas serotonin also goes up is the basolateral amygdala, bed nuclues of the stria terminalis (associated depression/ fear) and the medial Pre-frontal cortex
Whats the debate about how SSRI’s work?
*** email about this
Initially after taking them, people may get worse, or maybe something else happens at receptor level after 6 weeks
EITHER:
- Trick the pre-synaptic to make more like we initially thought - by thwarting the reuptaker
OR
- Because initially, there is constantly so much 5-HT in the synapse, there would be less receptors on the post-synpatic. But adding SSRI’s increase receptors We dont need to put much effort in catching it all so dont need many receptors
Not sure which way round the NT’s work in response to anti-depressants
- might be different for depression or anxiety
What is evidence against LH
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X - not all animals develop LH
X - Ronan (2000) Rats that did not develop LH had higher levels of Serotonin metabolites (5-HIAA) in their lateral septum - recyled serotonin quicker - not having it accumulate and stress out the system
X - depressed rats doing exercise
Outline the study into depressed rats doing exercise
Depressed rats doing exercise - 6 weeks voluntary wheel running
- exercising rats didnt feel LH
- this prevented depressed behavioural consequences of learned helplessness via:
•UP-REGULATED 5-HT1a receptors in dorsal Raphe nuclues went up
- reducing that overactivity of serotonin
•REDUCED BOTH RAPHE NUCLUES AND BED NUCLUES STRIA TERMINALS ACTIVITY (via decrease 5-HT2C excitatory receptors)
- so receptors also went down on top of activity of serotonin
Exercising reduces the impact of 5-HT on depression, and the amount of receptors you have
- need the optimal amount of Serotonin, not too much or not too little
What did Hammack (2012) find - social defeat etc
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The same stuff happens if you have:
•Chronic social defeat
•Chronic Inescapable shock
- influences the HPA - hypothalamus pituitary axis
- leads to elevated basal levels of Glucocorticosteroids
- seen in MDD
If you handle baby rats (Stressful for them), cortisol levels go up, but then cortisol responses get blunter, get less sensitive, CRH goes up (Cortico-steroid releasing hormone), this is bad for the immune system
How is this stuff linked to the immune system
Having a pessimistic explanatory style: immune system goes down
- having chronic elevation of Cortico-steroid releasing hormone (CRH) - higher CRH:
- associated with responses to stress, but if they stay elevated, it can be bad
- leads to frequent minor colds and major disease
- being constantly stressed can be bad for your immune system
Outline the summary
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- If you have a situation of unavoidable pain, no control and no escape, many animals will develop LH
- but those who can metabolise that excess serotonin away might not
- how quickly you metabolise serotonin is maybe your genetics but also your explanatory style - In these situations we see altered levels of NE/ 5-HT CORT activity
- resulting in a change of sensitivity - Consequences of a negative generalised cognition (explanatory style), if negative = increased risk of burnout, depression, inactivity, sickness
- Exercise can reset this (control/ reward)
- can down regulate receptors, making them less sensitive - Unclear if depression is just due to low ST and NE
- if anti-depressants might not work for you, if you are not good at metabolising serotonin away, this might increase to too high a level
- due to genetic differences. E.g. this treatment may not work for you as you are not a good metaboliser
