Lecture 15 (CNS Pharmacology IV- Antidepressant drugs)

Question 1

What are the two disorders associated with depression? (2)

Answer 1

-Unipolar depression
-Bipolar depression

Question 2

What is unipolar depression?
And what are the two types of it and what do they mean? (4)

Answer 2

Mood swings in negative direction

Reactive – caused by real life effects (75%)
Endogenous – without underlying cause (25%)

Question 3

What is bipolar depression?

Answer 3

Bipolar depression - mood swings, alternate between negative mood swings, and mania – self confidence impatience, aggression

Question 4

What are typical symptoms of depression? (7)

Answer 4

-Low mood (anhedonia), negative thoughts, misery, pessimism, irritability
-apathy: loss of interest in daily activities
-Severe loss or gain in weight/appetite
-Low self-esteem, feelings of worthlessness or guilt
-Sleep disturbance: insomnia or excessive sleeping
-Loss of appetite & libido
-Diminished ability to think/concentrate

Question 5

When is a patient diagnosed with clinical depression?

Answer 5

Subjective-qualitative: patients exhibit depressed behaviour for over 2 weeks and symptoms disrupt normal social and occupational function

Question 6

Describe the neural pathways which shows the effect of anti-depressants? (3)

Answer 6

-Nucleus accumbens (NAc) has an antidepressant effect on individuals who have treatment-resistant depression

-Stimulation of NAc means increased production of brain-derived neurotrophic factor (BDNF)

-Increased BDNF means decreased CREB (Cyclic AMP response element), associated with high levels of cortisol (stress and anxiety)

Question 7

What part of the brain shows fear?
What part of the brain do hormones effect?
produces dopamine?

Answer 7

-Amygdalla
-Hypothalamus
-Ventral tegmental area (VTA)

Question 8

Which two hormones guide appetite? (2)

Answer 8

-Ghrelin
-Leptin

Question 9

What is postnatal depression?

Answer 9

Babies brain waves can become altered if the
mother is depressed (usually for 2-8 weeks)

Question 10

What are the animal models for testing depression? (4)

Answer 10

-Water bath - how much they struggle in water

-Measuring social interaction - decreases in depression

-Learned-helplessness test - measures the development of passive responses to inescapable foot shock

-Intracranial self-stimulation - measures effort that an animal expends to stimulate brain reward circuits electrically

Question 11

What happens to animal in learned helplessness when they receive continuous electric shocks?

Answer 11

They stop trying to escape

(this changes with analgesic drugs)

Question 12

Which neurotransmitters are involved in depression? (3)

Answer 12

-Na (Noradrenaline) and 5HT (Serotonin) reduced
-BDNF/TrkB reduced neurogenesis
-NMDA over-activation (causes neurogenesis)

Question 13

What is the monoamine hypothesis of depression?

Answer 13

The cause of depression is a depletion in the levels of serotonin, norepinephrine, and/or dopamine in CNS

Question 14

What are the four types of anti-depressants? (4)

Answer 14

-Monoamine oxidase inhibitors (MAOIs eg. Phenylzine, moclobemide)

-Classical Tricyclic antidepressants (TCAs eg. imipramine) - blocks MOA uptake

-Selective serotonin(5-HT) reuptake inhibitors (SSRIs eg. fluoxetine) - changes levels of diff MOAs

-Monoamine Receptor Antagonists

Question 15

What do MAOIs (Monoamine Oxidase Inhibitors) do in type A and B? (2)

What is their side-effect?
What happens when combined with tyramine?

Answer 15

-MAOIs, inhibition of MAO type A produces anti-depressant effect, better at breakdown of noradrenaline and serotonin (type B inhibitors useful in Parkinson’s)

-Noradrenaline (NA) depletion in sympathetic terminals, causes postural hypertension

-Hypertension (cheese effect)

Question 16

What do TCA anti-depressants do?
What side-effects does it have?
What happens in overdose?

Answer 16

-TCAs inhibit neuronal reuptake of 5-HT and NA

-(mACh, dry mouth, blurred vision, constipation), adrenergic (a2 block, postural hypotension) and histaminergic (H1 block, sedation) effects

-Dangerous in overdose: confusion & mania, cardiac dysrhythmias

Question 17

What do SSRI anti-depressants do?

Answer 17

SSRIs specifically inhibit 5-HT re-uptake
less side effects & toxicity

(high degree of selectivity, less side-effects)

Question 18

What are functions of NA in CNS?

Answer 18

Functions –> arousal/attention, mood, blood pressure regulation, pain

(deficiency of NA pathways in brain leads to depression) - TCAs and MOAIs increase NA

Question 19

What are the functions of 5HT (serotonin) in CNS?

Answer 19

Functions –> Hallucinations, sleep and wakefulness, mood and emotion, feeding behaviour, sensory pathways and nociception, body temperature, vomiting

Anhedonia-the inability to gain pleasure from normally pleasurable experiences - 5-HT has role in regulating limbic processes so if not working causes this

Question 20

What type of processing do these have a role in?

-NA
-5HT

Answer 20

NA - sensory processing
5HT - limic processing

Question 21

How many subfamilies for 5HT are there?
which one is a target for antidepressants?

Answer 21

-7 subfamilies
-5HT1

Question 22

How does chronic treatment with anti-depressants affect BDNF (brain deprived neutrophil factor)?
What does BDNF do in regards to synaptic connections?

Answer 22

-Increases BDNF

-BDNF stabilizes synaptic connections

Question 23

What is the evidence in support of the monoamine hypothesis of depression? (3)

Answer 23

-Iproniazid, the first specific antidepressant, is an MAO Inhibitor

-Reserpine, which produces depression and parkinsonism, depletes stores of monoamine transmitters.

-Tricyclic ADs (originally synthesised in attempt to develop new antipsychotics) inhibit re-uptake of 5-HT and/or NA.

Question 24

What part go the brain do these come from? (3)

Dopamine -
Serotonin -
Noradrenaline -

Answer 24

Dopamine - Ventral Tegmental Area (VTA)
Serotonin - Dorsal Raphe
Noradrenaline - Locus Coureleus (LC)

Question 25

Which antidepressant is preferred TCAs or MAOs?

Answer 25

TCAs

Question 26

Why do antidepressants with 5-HT make you feel worse at first?

Answer 26

-Depression gets worse at first, we end up losing inhibitory receptors so we get increased neuronal activity and increase in neurotransmitter release, increased neural pathway function

Question 27

Why is there a slow action mechanism of SSRIs?

Answer 27

Need to desensitize somatodendritic 5HT1A receptors

Question 28

What does BDNF (brain deprived neutrophic factor) do?

Answer 28

Stabilises synaptic connections

(depression linked to lack of BDNF but knock out mutant of BDNF show no signs of depression) - shows how complex it is, multiple combinations

Question 29

What are the 3 main types of antidepressants? (3)

Answer 29

-TCAs
-MAOIs
-SSRIs