Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CNS > L1 Monoamine hypoth > Flashcards

L1 Monoamine hypoth Flashcards

1
Q

List the three core elements that relate to anxiety disorders

A

1) Negative cognition - interpret ambiguous stimuli negatively e.g. they’re looking at me so much be laughing at me
2) Physiological - seating, shaking, inc HR, stress, cortisol increase
3) Avoidance - don’t like to go into a room with lots of people - will be embarrassing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List 4 types of anxiety disorder

A

1) Panic disorder - panic attacks ‘might die’
2) Social anxiety disorder - speech, blush, embarrassment
3) GAD - general worry, tension, threat
4) PTSD - flashback to known event, trigger, 9/11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Benzodiazepines act at the _____ receptor.
They are sedative and anxiolytic and are fast acting (_ weeks)
They are safe but potential for ______.

A

GABAa
2
Dependence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Buspirone acts at _____ receptors (partial agonist)
Used in GAD
Lacks _____, ____ or abuse seen with benzos

A

5HT1a (auto receptors and also postsynaptic receptors)

Dependence, sedation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

SSRIs have a slow therapeutic onset (4-6 weeks) sertraline suggested as cost effective e.g.used in _ _ _

A

GAD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Beta blockers e.g. propranolol block peripheral/central _______ activity

A

Noradrenergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Atypical antipsychotics e.g rispiradone used as _____ therapy for treatment resistant OCD, PTSD

A

Adjunct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Talk through the monoamine theory of depression

A

Deficit in monoamine neurotransmitters e.g. 5HT, NA and DA.

5HT = obsession, anxiety, -ve cognitions
DA = combination with NA - appetite, other two - pleasure
NA = attention - with DA - appetite, 5HT - mood and sleep
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What’re the limitations of existing antidepressants?

A

Efficacy: <40% achieve remission from symptoms
Tolerability: SE’s deter use - emotional blunting, sexual dysfunction, nausea and vom
Time to onset: 4-6weeks - long time
Discontinuation effects: physical withdrawal - can’t just stop
Suicide risk: controversial in lit but might be due to giving motivation to get out of bed and carry out suicide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

5HT1AR - site of action of B_______
Polymorphisms in 5HT1Ar promoter alters expression levels (L___ & G_____, _____)
_____ 5HT1Ar levels in pts with panic disorder (N_______ et al _____)

A

Buspirone
Lesch & Gutknecht 2004
Neumeister et al 2004

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

5HT1Ar are GPCRs TRUE or FALSE

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Buspirone related compounds are gepirone and ipsapirone

  • It’s a _____ agonist
  • it’s as effective as ______
  • As fast acting as BZs (BUT controversial)
  • Lacks BZ side effects e.g. _____, ______
  • Has no ______ symptoms
  • Augment with _____ to activate 5HT1A receptor and desensitise it - so sensitise to SSRI treatment
A 
Partial 
Diazepam
Around 2 weeks
Sedation and cog impairment
Withdrawal 
SSRIs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Buspirone partial agonist at 5HT1Ar (GPCR) causes closing of ____ channels presynaptically to decrease NT release and causes opening of __ channels postsynaptically to elicit a slow hyperpolarisation. It also causes inhibition of _____ _____ so less ___ phosphorlyation.

A

Ca2+
K+
Adenylyl cyclase
PKA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

5HT1Ar located in _____ _____.
5HT neurones synapse onto non 5HT neurones in _____ e.g glutamatergic nerve cell.
5HT1A autoreceptors function physiologically as a sort of _______ feedback mechanism to regulate _____ release (sense levels of 5HT and adjust 5HT neurone firing to reduce transmitter release accordingly)

A

Raphe nuclei
Forebrain
Homeostatic
5HT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

5HT1A auto receptors are located on ____ and ____ of 5HT neurones. When they are stimulated they are coupled to gi/go ____ subunits and inhibitory 5HT cell firing through beta/gamma subunits. This reduces NT release.

A

Soma and dendrites

Alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Buspirone is a partial 5HT1Ar agonist and acts at postsynaptic receptors and 5HT1A auto receptors. Activating these receptors results in transiently _____ 5HT activation.

A

Less

17
Q

What happens if you infuse buspirone directly into amygdala of rats? What does this mean?

A

Induces anxiolytic effect so may not have effect at presynaptic receptor at all!

N.b. other 5HT receptors also have an effect on 5HT release not just 5HT1Ar

18
Q

Buspirone desensitisation:

  • On repeated exposure to agonist the GPCR will show reduced response as proportion of receptors, having been stimulated on 1st exposure are NOT capable of signalling on 2nd
  • So what happens when give buspirone?
A
  • Pre synaptic receptors exposed to buspirone and repeatedly exposed so causes 5HT neurones to reduce 5HT release
  • Eventually 5HT1Ar desensitises and buspirone fails to reduce 5HT firing rate hence the firing rate recovers
  • This reason suggests why buspirone takes a couple of weeks to have max, clinical effects
19
Q

Explain why SSRI’s have a delayed therapeutic effect?

A
  • SSRIs bind 5HT transporter (serotonin reuptake transporter) expressed somatodendritically and at synapses
  • In presence of SSRIs the transporters are blocked which leads to an increase in 5HT levels
  • Somatodendritically 5HT levels increase which activates 5HT1A autoreceptors and causes a transient decrease in 5HT neurone firing rate
  • BUT these 5HT1A auto receptors desensitise on repeated 5HT exposure
  • 5HT firing hence begins to recover and 5HT levels increase
  • This occurs over a period of weeks, hence why SSRIs MAY take this period of time to have a therapeutic effect
20
Q

SO ______ in 5HT neurone firing due to _____ auto receptor stimulation thought to contribute to delay in ____ and _____ therapeutic effects.

A

Decrease
5HT1A
SSRI and Buspirone

21
Q

How can you utilise desensitisation?

A
  • Aim to ‘speed up’ desensitisation by using a ‘better buspirone’ or don’t allow desensitisation to occur at all and just block receptor instead

better buspirones e.g. gepirone, ipsapirone, flesinoxan

22
Q

Presynaptic raphe 5HT1A receptors and postsynaptic hippocampal receptors both desensitise TRUE OR FALSE

A

FALSE

Presynaptic 5HT1Ar in the raphe desensitise BUT postsynaptic hippocampal receptors do not desensitise

23
Q

Suggest a way of speeding up SSRI effects - name specific drugs…

A
  • Augmentation with SSRI and pindolol (5HT1Ar antagonist with selectivity for presynaptic receptors)
  • Pindolol binds 5HT1Ar and prevents desensitisation from occurring and from 5HT neurone firing
  • This speeds up the onset of SSRI action as the level of 5HT remains high w/o auto receptor stimulation

REF: Seagrave and Nathan 2005

24
Q

List 4 new antidepressants and briefly discuss MOA.

A

Desvenlafaxine
- SNRI
Trazodone extended release
- SSRI and 5HT2a/c antagonist extended relase
Vortioxetine
- SSRI and partial 5HT1Ar partial agonist
- SPARI - serotonin partial agonist reuptake inhibitor
Vilazodone
- Multi-modal antidepressant
- Reuptake inhibitors & 5HT1A, B, 5HT 3&7 agonists
- Speeds up onset and more efficacious than SSRIs

25
Q

What evidence is there for the role of 5HT1A receptor in anxiety? Human and animal model references

A
  • Polymorphisms in human 5HT1Ar promoter regulating expression levels leads to altered level of 5HT1ar - (Lesch & Gutknecht 2004)
  • Decreased 5HT1Ar seen in patients with panic disorder (Neumeister et al 2004)
  • 5HT1A receptor is the site of action for anxiolytic buspirone - buspirone acts to decrease symptoms of anxiety in around 2 weeks
  • Is as effective as diazepam

CNS (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions