Lecture 15 - antidepressants

Question 1

what is unipolar depression?

Answer 1

• mood swings always in the same direction
• reactive (75%) associated with stressful life and accompanied by anxiety, agitation.
• endogenous (25%) is unrelated to external stress
• both treated same way

Question 2

what is bipolar disorder?

Answer 2

• depression alternates with mania characterised by excessive exuberance, enthusiasm, self-confidence is combined with irritability, impatience and aggression.
• bipolar is hereditary

Question 3

symptoms of depression?

Answer 3

• low mood (anhedonia), negative thoughts, misery
• apathy (loss of interest in daily activities)
• severe weight loss/gain
• low self-esteem
• sleep disturbance

Question 4

what is the diagnosis for depression?

Answer 4

• caused by stressful life events and genetic risk (40%)
• secondary to illness (cushing’s) side effect of a drug
• patients have depressed behaviour for more than 2 weeks

Question 5

what brain regions have an antidepressant effect?

Answer 5

deep brain stimulation of subgenual cingulate cortex or nucleus accumbens has an antidepressant effect on individuals after treatment. Mediated by inhibiting activity of these regions

Question 6

action of brain-derived neurotrophic factor (BDNF)

Answer 6

BDNF within mesolimbic dopamine circuit mediates social stress, through activation of transcription factor CREB through phosphorylation

Question 7

what is the importance of the amygdala?

Answer 7

shown to be important limbic node for processing emotionally salient stimuli like fearful faces

Question 8

what does stress cause?

Answer 8

decreases concentrations of neurotrophins (BDNF). decreased activity of CREB result from high levels of cortisol which is the stress hormone released from adrenal cortex

Question 9

what does metabolic hormones produce?

Answer 9

ghrelin and leptin produce mood-related changes through their effects on hypothalamus and several limbic regions

Question 10

what is the effect of postnatal depression?

Answer 10

happens shortly after giving birth and the children of the mother are more likely to have depression

Question 11

what is the acute stress animal model of depression?

Answer 11

• behaviours caused by some conditions that trigger human depression.
• forced-swim test quantifies immobility in a water bath. antidepressants increase escape behaviour.
• model used for coping behaviours

Question 12

what is the chronic stress animal for depression?

Answer 12

• shows structural, transcriptional and epigenetic changes in several brain changes.
• learned helplessness is where rodents are exposed to repeated inescapable foot shock resulting in failure to escape and depression.
• animals have stressful stimuli over a 2 week period

Question 13

what is the monoamine hypothesis?

Answer 13

depletion of monoamine transmitters (noradrenaline and serotonin) causes depression. drugs like reserpine can cause this.

Question 14

what neurotransmitters promote neurogenesis?

Answer 14

serotonin and noradrenaline through their 5HT1A receptors and alpha2 adrenoreceptors via BDNF. BDNF binds to TrkB receptors

Question 15

what does over activation of glutamatergic NMDA cause?

Answer 15

neuronal degeneration

Question 16

how does iproniazid support the monoamine hypothesis?

Answer 16

first specific anti-depressant, acting as a monoamine oxidase inhibitor and increases central noradrenergic and serotonergic transmission

Question 17

how does reserpine support monoamine hypothesis?

Answer 17

produces depression and parkinsonism, depletes stores of monoamine transmitters

Question 18

antidepressant drugs

Answer 18

• monoamine oxidase inhibitors e.g. phenylazine
• tricyclic antidepressants (TCA) e,g, imipramine
• selective serotonin reuptake inhibitors e.g. fluoxetine

Question 19

action of MAO inhibitors

Answer 19

type A (NA and serotonin) produces anti-depressant effect
type B is useful in parkinson’s
- produce rapid and sustained increase of serotonin

Question 20

what are the side effects of MAO inhibitors?

Answer 20

cause postural hypotension because of the noradrenaline depletion in sympathetic terminals

Question 21

what causes the hypertension?

Answer 21

combined with dietary sources of tyramine (cheese,wine) is not being broken down by MAO because of MAOIs. this problem avoided by reversible MAO inhibitor moclobemide.

Question 22

what are the dangers of tricyclic antidepressants (TCA)

Answer 22

in overdose causes excitement, convulsions and then a coma with respiratory depression (increased by alcohol), cardiotoxicity due to block of HERG channels

Question 23

action of antidepressants (TCA)

Answer 23

inhibit neural reuptake of NA and serotonin

Question 24

side effects of TCA

Answer 24

associated with anticholinergic (dry mouth, blurred vision and constipation.
in adrenergic system the side effects are postural hypotension and histaminergic causing sedation

Question 25

what does excessive central stimulation of noradrenergic pathways in CNS cause?

Answer 25

leads to tremors, excitement, insomnia and in overdose convulsions happen
side effects are increased appetite and weight

Question 26

what is the precursor to serotonin?

Answer 26

tryptophan - an essential amino acid in protein rich foods and chocolate as well as dietary supplements

Question 27

what are the side effects of SSRI’s?

Answer 27

nausea, insomnia and sexual dysfunction but there is less sedative effects then TCA’s and less antimuscarinic effects

Question 28

what serotonin receptor is the only ligand gated?

Answer 28

5HT3

Question 29

what serotonin receptors are Gi(inhibitory)

Answer 29

5HT1 and 5HT5

Question 30

what serotonin receptors are Gq (phosphorylation)

Answer 30

5HT2

Question 31

what serotonin receptors are Gs?

Answer 31

5HT4,6 and 7

Question 32

what is the action of SSRIs?

Answer 32

bind to p glycoprotein - molecule in BBB to transport drugs back into bloodstream. they inhibit neurotransmitter release by serotonin