lecture 4 - communication at the synapse 2

Question 1

biogenic amines neurotransmitters

Answer 1

-dopamine
-serotonin
-histamine
-adrenaline/epinephrine
-noradrenaline/norepinephrine

-all small molecule neurotransmitters
-similar structures
-widespread in the brain (so if prescribed a drug that acts on these, you should be aware side effects can be widespread)

Question 2

unconventional neurotransmitters

Answer 2

endocannabinoids

Question 3

serotonin
-structure
-where is most of this
-where is it produced
-its roles

Answer 3

-90% serotonergic signalling is in gut
(works to have an effect on digestion)
-10% serotonergic neurons in the brain

-produced in the pons and upper brainsteam (raphe nuclei) , it has projections to the forebrain

-roles: regulation of mood, appetite and sleep, also involved in memory and learning

Question 4

serotonin cascade
-serotonin precursor

Answer 4

-single neurotransmitter from its precursors to its final version

-serotonin precursor is tryptophan, mainly taken in by our diet eg oats, fish, cheese
-tryptophan converted to 5htp and then converted to serotonin
-packaged into vesicles, released from the presynaptic neuron to receptors on post synaptic neuron
-action potential which arrives at presynaptic neuron causes cell to release
-

Question 5

depression and monoamines
key features

Answer 5

-intense feelings of sadness, helplessness and hopelessness

-anhedonia- general lack of interest that you would usually enjoy

-tiredness, lack of energy
-abnormal sleep and eating patterns

-cognitive impairments: concentrations, memory, executive function

Question 6

the monoamine hypothesis
-how did we come about linking depression to monoamines

Answer 6

-came about from observing side effects of drugs
-reserpine (hypertension medication)
-in 1960s people who took this for blood pressure started to develop depression symptoms (micheals and gibbon 1963)

Question 7

what is reserpine
-how can it explain monoamines link to depression

Answer 7

-reserpine is antagonist (which reduce normal action of drug) of the monoamines
-so suggests that monoamines are to low in patients who have depression

-reserpine prevents monoamines from being packaged into the vesicles , so nothing to release and so less monoamine action

Question 8

what category of drug may be used in treatment of depression

Answer 8

agonists - antidepressants

Question 9

types of antidepressants

Answer 9

-monoamine oxidase inhibitors
-tricyclic antidepressants
-SSRIs
-SNRIs

Question 10

monamine oxidase inhibitors (MAOIs)
-what does it do

Answer 10

-inhibit the activity of the enzyme called monoamine oxidase that normally breaks down monoamine NTs- dopamine, noradrenaline and serotonin
-so leaves more of the molecule you need

-have to be careful with diet since it can mess with noradrenaline

Question 11

tricyclic antidepressants

Answer 11

-work on noradrenalin and serotonin
-block reuptake of noradrenaline and serotonin-increasing levels of these two NTs in the synapse

Question 12

SSRIs

Answer 12

-selective serotonin reuptake inhibitors : first choice for treating depression
eg prozac

Question 13

SNRIs

Answer 13

selective noradrenaline reuptake inhibitors

Question 14

serotonin based treatments
-SSRis process
-side effects
-examples

Answer 14

-selective serotonin reuptake inhibitors block the channels that allow serotonin to be removed from the cleft

-side effects :due to high levels of serotonin receptors in the GI tract, side effects of treatments can include weight loss, nausea and diarrhoea

-prozac fluoxetine are examples

Question 15

agonists _____ serotonin action

Answer 15

enhance

Question 16

does depression occur only due to low serotonin
moncrieff 2022

Answer 16

-paper found no strong evidence for lowered serotonin actions in depressed patients compared to controls
-royal collge of psychiatrists 2019
saying that ‘anti depressants correct a chemical imbalance is an over simplification’

Question 17

the timing of effects of ssris
stahl 2000 experiment

Answer 17

-had 316 patients with major depressive disorder
-split into groups
-one group given placebo
-one group had sertraline
-one group citalopram

-two ssri effects measured on Hamilton depression rating scale, and results showed mood getting better

-randomised, double blind and placebo controlled study. so good study

-citalopram took longer to show effect
-when taking these serayonin goes up within hours (if you were to measure) But mood doesnt just change

Question 18

evidence that anti depressants are effective for some patients
-cipriani et al 2018

Answer 18

-a study of antidepressants found all studied drugs to be more effective than placebo
-3 ssris in particular (escitalopram, paroxetine and sertraline) found to have the highest response/lowest drop out rates
-is it doing more than just increasing seratonin levels?

Question 19

cognitive mechanisms causing depression

Answer 19

-could have a role in causing depression
-negative automatic thoughts
-negative schema
-negative information processing biases

negative biases in processing
-information recall
-interpreting facial expressions (more likely to interpret it as negative)
-distraction by negative stimuli

-emotional Stroop and negative bias

Question 20

ssri can influence cognition
-face recognition
-memory

Answer 20

-in depressed participants, following a single dose of ssris we find
-enhanced recognition of facial expressions (tranter et al 2009)
particularly hapiness
-increased recall of positive stimuli in word memory tasks (harmer et al 2009)

no associated increase in self reported mood

Question 21

acute effects of antidepressants
-how are these findings consistent with cognitive theories of depression

Answer 21

-acute affects of antidepressants are found for processing emotional stimuli
:
-reduced negative bias in attention and memory tasks , enhanced recognition of facial expressions
-findings are consistent with cognitive theories of depression: negative low level biases in perception and attention are related to high level beliefs about self, world and others (becks dysfunctional schemas)
-someone with depression has dysfunctional schemas, caused by negative attention bias

-acute cognitive affects occur with no reported change in mood

-suggested that antidepressants have an effect on cognitive level and gradually over a few weeks they’ll have a noticeable effect in mood
-suggested that combining cbt and antidepressants is effective

Question 21

dopamine
-produced by ?
-involved in pathways

Answer 21

-produced by tyrosine which is then converted into DOPA and then converted into dopamine
-dopamine is involved in multiple pathways in the brain

Question 22

dopamine
-key functions
-the four pathways

Answer 22

-key importance in many functions , including reward, movement and the release of hormones
-four pathways
-nigrostriatal
-tuberoinfundibular
-mesocortical
-mesolimbic

Question 23

dopamine: the tuberoinfundibular pathway

Answer 23

-shortest pathway
-moves from arcuate nucleus of the hypothalamus to the pituitary gland
-has a restraining affect on the gland
-influences release of hormones into the blood stream
-eg growth hormone, adrenocorticoids, prolactin (production of milk)
-pituitary gland further controls hormone release

Question 24

dopamine: the nigrostriatal pathway

Answer 24

-pathway from substantia nigra to striatum
-involved in the basal ganglia loop and the initiation of movement
-the pathway affected in Parkinson’s disease

Question 25

dopamine : the mesocortical pathway

Answer 25

-starts ventral tegmentum at the brain stem to frontal lobes

-involved in motivation and emotional responses

-decreased levels of dopamine in this pathway are thought to be associated with the negative symptoms of schizophrenia

-apathy, listlessness, poverty of speech

Question 26

dopamine : the mesolimbic pathway

Answer 26

• Ventral tegmentum to the limbic system, via nucleus accumbens,amygdala, hippocampus and medial prefrontal cortex
• Associated with feelings of rewardand desire
• Implicated in addiction and depression
• Hyperactivity of dopamine associated with the positive symptoms of schizophrenia (e.g. delusions,hallucinations)

Question 27

Schizophrenia

Answer 27

a psychotic disorder involving disturbances of thought, emotion and behaviour
literally a ‘split mind’ (but not split personality)
-‘fragmented thinking’
-‘a disconnect between a persons subjective experiences and objective reality’

Question 28

symptoms of schizophrenia

Answer 28

Positive symptoms = presence of abnormal experiences & behaviour (e.g. hallucinations, delusions,disorganized speech & behaviour)

• Negative symptoms = absence of normalexperiences & behaviour (e.g. lack of emotion, apathy,anhedonia, social withdrawal, poverty of speech)
• Cognitive symptoms = broad impairments in attention,working memory, episodic memory, executive functions

Question 29

the dopamine hypothesis of schizophrenia
-how does dopamine link to schizphrenia

Answer 29

-the link between dopamine and schizophrenia came about by observing side effects from other drugs

-dopamine agonists (eg amphetamine, cocaine
-producing schizophrenia like symptoms in previously healthy individuals
-worsen symptoms in people who have been diagnosed with a psychotic disorder

Question 30

what does the dopamine hypothesis of schizophrenia say

Answer 30

-psychosis (positive symptoms) are caused by excessive levels of dopamine

Question 31

dopamine agonists
-amphetamine and cocaine
-what do they do
-what does chronic abuse of this do

Answer 31

-they increase release and or block reuptake of dopamine
-amphetamine has dual action, it can increase how much dopamine is release in the first place

-chronic abuse of these can cause schizophrenua like symtoms (paranoia, delusions,hallucinations,stereotyped repetitive and complusive behaviours

Question 32

dopamine agonist
L dopa

Answer 32

-an artificial version of a dopamine precursor
-used to treat parkisons disease
-high dose of this can increase amounts of dopamine made so cause dopamine like symptoms in patients

Question 33

dopamine antagonists
anti psychotics

Answer 33

-anti psychotics used to treat positive (i.e psychotic) symptoms like hallucinations and delusions
-chlorpromazine/thorazine
-haloperidol

antipsychotic have no effect on negative symptoms, and can actually make these worse
-they block dopamine receptors (specifically type D2) preventing their activation

Question 34

what about negative symptoms schizophrenia

Answer 34

Original formulation of the dopamine hypothesis didn’t address negatives symptoms

• Current versions regard schizophrenia as a disorder of dopamine regulation –
• Positive symptoms are linked to excessively high levels of dopamine, especially in basal (‘deep’) forebrain areas
• Negative symptoms may reflect abnormally low levels of dopamine (&reduced brain activity) in PFC – this would explain why antipsychotic drugs can worsen negative symptoms

Question 35

dopamine regulation

Answer 35

One version of this idea (e.g.Davis et al, 1991) sees dopamine under-activity in prefrontal cortex as the primary deficit in schizophrenia

• This then leads to reduced inhibitory control over dopamine producing neurons in basal forebrain areas(‘mesolimbic system’)
• ‘Runaway’ dopamine release in basal forebrain /mesolimbic areas then leads to positive symptom

Question 36

schizophrenia
complementary therapies

Answer 36

-antipsychotic drugs don’t necessarily prevent hallucinations or delusional thoughts
-but can make them feel less important and less distressing

psychotherapy (eg CBT) may be required to actually change delusional beliefs

but this is more likely to succeed if combined with an antipsychotic to weaken ‘attachment’ to delusional beliefs
-treatment for negative symptoms may involve medication but has also been found to benefit from CBT (eg elis et el 2013)

Question 37

the side effects of dopamine treatments
agonists
antagonists

Answer 37

Due to the widespread dopaminergic synapses, any treatment involving these dopamine receptors will have the potential for side effects

• Agonists of dopamine: Drugs for Parkinson’s treatment can cause hallucinations, psychosis; impulse control disorders- compulsive gambling, shopping, binge eating (acting on the mesolimbic and mesocortical pathways)
• Antagonists of dopamine: Anti-psychotics can cause Parkinsonism(Parkinson’s like symptoms); tremors and dystonia (acting on the nigrostriatal pathway)Increased secretion of prolactin, leading to galactorrhea (unusual secretion of breast milk) (acting on the tuberoinfundibular pathway)

Question 38

unconventional neurotransmitter

Answer 38

Must be present in pre-synaptic terminal, stored in synaptic vesicles. NO
* These NTs are not stored in the pre-synaptic terminal

• Must be released into the presynaptic cleft in response to Ca2+increase. NO
• They are not released by exocytosis and may not be released from the terminal at all
• Must have an effect on specific receptors on the post-synaptic neuron. NO
• They may be used in retrograde signalling: the post-synaptic cells ignals back to the pre-synaptic cell

Question 39

endocannabinoids

Answer 39

Produced ‘on-demand’ from the cell membrane (not stored in vesicles)

• Retrograde signalling: post-synaptic cells signal to pre-synaptic neurons
• Their release reduces the amount of conventional neurotransmitters released for a short period
• Allows post-synaptic cell to control its ‘incoming traffic’
• Role in synaptic plasticity (Vaughan & Christie, 2005)
• Involvement in memory, regulation of appetite, homeostasis