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Psychopharmacology > GABA > Flashcards

GABA Flashcards

1
Q

GABA synthesis

A

Glutamine –> Glutamate
ATP needed and glutaminase
Glutamate –> GABA
glutamic acid decarboxylase (GAD)

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2
Q

what inhibits GABA synthesis?

A

allyglycine

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3
Q

Describe GABA NT

A

most common inhibitory NT in brain

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4
Q

what is used as a marker for gabaergic neurons?

A

GAD

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5
Q

10-40% GABA Location

A

cortex
hippocampus
substantia nigra

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6
Q

types of neuron projections

A

projection neurons and interneurons

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7
Q

GABA plays a role in what?

A

motor control

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8
Q

Describe GABA at synapse

A
  1. VGAT/VIAAT package GABA into vesicles, then released into synaptic cleft
  2. GAT reuptakes GABA and brings either to astrocyte of presynaptic neuron
  3. If brought to astrocyte:
    - GABA-T breaks down GABA into Glutamate
    -Glutamine synthetase breaks down Glutamate into Glutamine
    -Glutamine is transported back to presynaptic neuron
  4. If brought to presynaptic neuron:
    - GABA-T breaks down GABA into succinate and glutamate (as byproduct)
    - or GABA is repackaged into vesicles
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9
Q

What inhibits GABA-T breakdown in astrocyte?

A

vigabatrin

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10
Q

What inhibits reuptake of GABA into presynaptic neuron?

A

tiagabine

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11
Q

What does VGAT/VIAAT do?

A

package GABA into vesicles

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12
Q

What does GAT do?

A

transports GABA to astrocyte or presynaptic neuron

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13
Q

What does GABA-T do?

A

breaks down GABA to succinate and glutamate

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14
Q

what breaks down glutamate into glutamine?

A

glutamine synthetase

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15
Q

Describe GABA-A receptors

A
  1. ionotropic
  2. open Cl channels = hyperpolarization
  3. 5 subunits
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16
Q

Describe GABA-B receptors

A
  1. metabotropic
  2. open K channels = hyperpolarization
  3. found post and presynaptically
    presynaptic: act as autoreceptors by inhibiting Ca channels
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17
Q

What is the reason behind different subunits for GABA-A receptors?

A

different subunits make ups affect which substances can bind

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18
Q

what is the most common subunit for GABA-A receptors makeup in the brain?

A

2(a1), 2(b2) 1(y2)

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19
Q

What is an antagonist for GABA-A receptors?

A

bicuculline

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20
Q

name 6 anxiety disorders

A
  1. Generalized Anxiety Disorder
  2. Panic Disorder
  3. Social Anxiety
  4. Phobias
  5. PTSD
  6. OCD
21
Q

What are the similarities of Fear and Anxiety?

A

overlapping neurocircuitry: amygdaloid complex
- key brain region responding to threatening events
1. Central Nucleus (hypothalamus, midbrain, pons, medulla): fight or flight
2. Lateral Nucleus (PFC, hippocampus, ventral striatum): learning about threatening events

22
Q

Differences between anxiety and fear

A
  1. BNST: overactivation in anxiety
  2. PFC: inhibitory control decreases activity in fear circuits
23
Q

NT involved in anxiety

A
  1. GABA
  2. Neurosteroids
  3. CRF
  4. NA
  5. 5HT
  6. DA
24
Q

How does GABA affect anxiety behaviours?

A
  1. activation of local GABA circuits lead to lower amygdala activity and lower stress
  2. inhibition of GABA-A receptor will cause an increase in anxiety
  3. GABA-A receptors need activation in order to have anxiolytic effects of BZD
25
How does neurosteroids affect anxiety?
1. cholesterol --> steroid hormone 2. bind to separate site of GABA-A receptor and increases duration of open Cl channels 3. lower neurosteroids will cause higher anxiety
26
How does CRF affect anxiety?
1. hypothalamic-pituitary-adrenal axis 2. CRF NT projections to locus coeruleus 3. higher CRF = higher anxiety
27
How does NA affect anxiety?
1. activation of LC releases NA and increases anxiety 2. NA in ANS leads to fight or flight 3. consolidates memory formation
28
How does 5HT affect anxiety?
1. agonists of 5HT receptor will lower anxiety 2. After repeated exposure to stressors, 5HT receptors become desensitized
29
How does DA affect anxiety?
1. stressors activate mesocorticolimbic DA system DA has inhibitory affects on PFC and GABA circuits in amygdala
30
4 drugs involved as pharmacotherapies for anxiety
1. SSRIs 2. BZDs 3. Barbiturates 4. Neurosteroids
31
describes SSRIs in use for anxiety
1. block SERT increasing 5HT 2. addresses both anxiety anddepression 3. high TI 4. Time delay
32
describe BZDs in use for anxiety
1. positive allosteric modulator of GABA-A 2. better TI than barbiturates 3. abuse potential 4. BZD and alpha 1 subunit associated with sedative effects 5. no suppression of breathing 6. no metabolic tolerance 7. competitive antagonist exists in case of overdose
33
What is the competitive antagonist for BZDs?
flumazenil
34
describes barbiturates in use for anxiety
1. positive allosteric modulator of GABA-A receptor 2. high abuse potential 3. low TI 4. increase CL opening in absence of GABA 5. tolerance
35
describe neurosteroids in use for anxiety.
1. sex hormones 2 allosterically modulate GABA-A receptor (+ or -) 3. used for treatment of post-partum depression
36
GABA-A receptor antagonist have what properties?
convulsant
37
what's one genetic reason people have epilepsy
mutations of GABA-A receptor
38
Seizures are caused by what?
over activation of glutamate or underactivation of GABA
39
how does underactivation of GABA lead to seizures?
theres a shift in CL ion concentrations that lead to a higher efflux out of the cell
40
what condition is not effective by BZD for seizures
status epilepticus
41
why are BZD ineffective for those with status epilepticus and what is the treatement?
1. downregulation of GABA-A receptors 2. Neurosteroids that target GABA-A receptors found in extrasynaptic regions
42
What is Catamenial Epilepsy?
seizures influenced by menstrual cycle
43
what is the reason behind catamenial epilepsy?
1. neursoteroids are made from progesterone 2. lower levels of progesterone = lower levels of neurosteroids = higher chance of seizure
44
sleepyness is triggered by what?
GABA release
45
Treatments that have been used for insomnia
1. CBT 2. opium, scopolamine, barbiturates, BZD
46
what are the complications with BZD for treatment of insomnia?
1. pharmacodynamic tolerance 2. loss of muscle coordination 3. long half life = hangover effect 4. amnesia 5. abuse potential
47
What is used instead of BZD for insomnia?
Z drugs
48
what are Z drugs?
positive allosteric modulators of GABA-A receptor - bind to same site as BZD - have a higher affinity for alpha 1 subunit of receptors - rapid onset - shorter half lives - side effects
49
What are BZD?
anxiolytic and sedating drug allosteric binding that increases or decreases receptor response to agonists like GABA

Psychopharmacology (4 decks)

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