lecture 4 - communication at the synapse 2 Flashcards
biogenic amines neurotransmitters
-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)
unconventional neurotransmitters
endocannabinoids
serotonin
-structure
-where is most of this
-where is it produced
-its roles
-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
serotonin cascade
-serotonin precursor
-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
-
depression and monoamines
key features
-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
the monoamine hypothesis
-how did we come about linking depression to monoamines
-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)
what is reserpine
-how can it explain monoamines link to depression
-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
what category of drug may be used in treatment of depression
agonists - antidepressants
types of antidepressants
-monoamine oxidase inhibitors
-tricyclic antidepressants
-SSRIs
-SNRIs
monamine oxidase inhibitors (MAOIs)
-what does it do
-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
tricyclic antidepressants
-work on noradrenalin and serotonin
-block reuptake of noradrenaline and serotonin-increasing levels of these two NTs in the synapse
SSRIs
-selective serotonin reuptake inhibitors : first choice for treating depression
eg prozac
SNRIs
selective noradrenaline reuptake inhibitors
serotonin based treatments
-SSRis process
-side effects
-examples
-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
agonists _____ serotonin action
enhance
does depression occur only due to low serotonin
moncrieff 2022
-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’
the timing of effects of ssris
stahl 2000 experiment
-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
evidence that anti depressants are effective for some patients
-cipriani et al 2018
-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?
cognitive mechanisms causing depression
-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
ssri can influence cognition
-face recognition
-memory
-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
acute effects of antidepressants
-how are these findings consistent with cognitive theories of depression
-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
dopamine
-produced by ?
-involved in pathways
-produced by tyrosine which is then converted into DOPA and then converted into dopamine
-dopamine is involved in multiple pathways in the brain
dopamine
-key functions
-the four pathways
-key importance in many functions , including reward, movement and the release of hormones
-four pathways
-nigrostriatal
-tuberoinfundibular
-mesocortical
-mesolimbic
dopamine: the tuberoinfundibular pathway
-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