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202- Theme 1 > How drugs control the brain > Flashcards

How drugs control the brain Flashcards

1
Q

Describe the GABAergic system

A

Widespread distribution in brain
Inhibitory interneurons- to keep excitatory in check
synaptic inhibition tightly regulated

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2
Q

What are the properties of Projection neurons?

A

Type of interneuron
long axes
usually glutamate
cerebellar purkinje cells= GABAergic projection neuron

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3
Q

What are the properties of Local interneurons?

A

bi-tufted
contained within CNS
connect other neurons
mostly GABA

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4
Q

What are the properties of GABA A ionotropic receptors?

A

ligand gated Cl channel- hyperpolarises neuron
Fast IPSP
Mainly GABAergic interneurons
Gated by GABA binding

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5
Q

What are the properties of GABA B Metabatropic receptors?

A

GPCRs
Indirectly coupled to K or Ca channels via 2nd messengers
Slow IPSP
Both pre and post synaptic

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6
Q

What is Baclofen used to treat and how?

A

Used as a muscle relaxant to decrease spasticity in Huntington’s

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7
Q

What are the 2 direct agonist and antagonists of the GABA A receptor?

A

Muscimol: agonist
Bicuculline: antagonist

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8
Q

What is benzodiazapene?

A

An indirect agonist of the GABA A receptor.
Increases frequency of channel opening
Used as anxiolytic and hypnotic drug
decreases anxiety, causes sedation, relaxes muscles

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9
Q

What outcome does blocking the GABA A receptor have?

A

Seizures

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10
Q

What is Barbiturates?

A

Indirect agonist of GABA A receptor.
Increase duration channel opening
used in anaesthesia and epilepsy treatment
Binds at different site to benzo’s but has same effect

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11
Q

What is the effect of alcohol at the GABA A receptor?

A

Indirect agonist. Interacts with NMDA, glycine, nicotinic and serotonin receptors
low doses= mild euphoria, anxiolytic effects
high doses= incoordination and amnesia

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12
Q

Where do excitatory glutamate neurons act?

A

Primary route of sensory and motor info and relay neurons between brain areas

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13
Q

Where do inhibitory GABA neurons act?

A

As interneurons- maintaining balance between excitation and inhibition

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14
Q

What are the diffuse modulatory systems?

A

A specific population of neurons that project diffusely and modulate GABA and glutamate activity in their target areas

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15
Q

What are the 6 diffuse modulatory systems?

A 
Dopaminergic 
Serotinergic
Noradregergic
Histaminergic 
Cholinergic 
Adrenergic
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16
Q

What are the 3 main Dopaminergic system and what is their function?

A
  1. Nigrostriatal system- (75% of brain DA) MOTOR control
  2. Mesocortical- behavioural effects
  3. Mesolimbic- innervates limbic parts
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17
Q

What type of receptors are dopaminergic receptors?

A

Metabotropic

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18
Q

What are the 2 subtypes of dopaminergic receptors

A

D1-like: D1 and D5. Gs- postsynaptic

D2-like: D2,3,4. Gi- pre and postsynaptic

19
Q

Describe the dopaminergic nigrostriatal system

A

cell bodies in substantia nigra project into the striatum (caudate nucleus and putamen)= important parts of basal ganglia involved in movement

20
Q

What disorders can dysfunction of the nigrostriatal system cause?

A

Parkinson’s: destruction of DA projections from SN to basal ganglia
Huntington’s: destruction of DA target neurons in striatum

21
Q

What drugs can be used to treat disorders of the nigrostriatal system?

A
  • L-dopa: passes through BBB
  • MAO inhibitors: stops breakdown in synaptic cleft
  • DA receptor agonists: act like DA
22
Q

Describe the mesolimbic system

A

cell bodies in ventral tegmental area project into limbic system, nucleus accumbens.
role in reinforcement of several stimuli

23
Q

What disorders can cause dysfunction of mesolimbic system?

A

Addictions: most drugs of abuse increase DA release in NAcc.
Short term: increase alertness and self-confidence. mimics activation of sympathetic nervous system
long term: natural rewards increase DA transmission and lead to reinforcement of associated behaviours. increase DA by cocaine shortcuts this pathway. Drug taking behaviour becomes reinforced= down regulation of endogenous DA system.
leads to craving drugs not natural rewards

24
Q

Describe the mesocortical system

A

VTA projection to frontal cortex.

Role in functions such as working memory and planning

25
Q

What disorders can cause dysfunction of the mesocortical system?

A

Schizophrenia: poor working memory and planning ability

26
Q

What drugs can be used to treat schizophrenia and dysfunction of the mesocortical system?

A

antipsychotics: chlorpromazine + haloperidol
- DA Receptors antagonists
- increase DA turnover, lose autoreceptor inhibition
- blockade of post-synaptic receptors- up-regulation
- extrapyramidal side effects
atypical antipsychotics: clozapine
- specific to receptor subtype
- clozapine- specific to antagonise D4 (cortex only)
- get decreased psychosis without EPS

27
Q

Describe the serotonergic system

A

9 raphe nuclei in reticular formation with diffuse projection
fire tonically during wakefulness, quiet in sleep
descending projections to cerebellum and spinal cord- pain perception
ascending reticular activating system with locus coeruleus
dorsal and medial raphe project through cerebral cortex

28
Q

What does the serotonergic system function in?

A 
Mood
sleep 
pain 
emotion 
appetite
29
Q

What drugs can be used to treat dysfunctions of the serotonergic system?

A

SSRIs (fluoxetine): increase serotonin function by inhibiting its reuptake. treatment for depression and anxiety

30
Q

How does MDMA affect the serotonergic system?

A

Causes serotonin and norepinephrine transporters to run in reverse. Increase release of serotonin and block reuptake

31
Q

How does LSD affect the serotonergic system.

A

Potent agonist at serotonin receptor in raphe nucleus. causes dreamlike state with altered sensory perceptions

32
Q

Describe the noradrenergic system

A

Projections from locus coeruleus throughout the brain
Role in arousal and attention
Receptors are metabatropic. alpha and beta adrengergic

33
Q

Describe the adrenergic system

A

Primarily in lateral tegmental area projecting to thalamus and hypothalamus.
Act on alpha and beta adrenergic receptors

34
Q

Describe the cholinergic system

A

In basal forebrain complex giving cholinergic innervation at hippocampus and neocortex. Controls memory and higher cognitive functions
Brain stem complex innervates dorsal thalamus and telencephalon. Controls excitability of sensory relay neurons of cholinergic link between brain stem and basal forebrain complex
In the periphery: Ach at NMJ and synapses in autonomic ganglia

35
Q

How is myasthenia gravis caused

A

autoimmune disease- destroys cholinergic receptors in muscle causing weakness and eventual loss of muscle activity

36
Q

How is Alzheimer’s disease caused

A

loss of cholinergic neurons in basal ganglia- possibly underlies memory deficit

37
Q

How is autosomal dominant nocturnal frontal lobe epilepsy caused?

A

associated with mutations in nicotinic receptor genes

38
Q

What is the effect of acetylcholinesterase inhibitors

A

prolong action of Ach at the synapse. Treatment for Alzheimers: physostigmine
Myasthenia gravis: neostigmine

39
Q

How does BOTOX work

A

prevents release of ACh at NMJ

40
Q

How does latrotoxin work?

A

permanent release, depletes ACh at NMJ

41
Q

What are the types of muscarinic cholinergic receptors?

A

Metabatropic receptors:

  1. muscarine- agonist
  2. atropine- antagonist
42
Q

What are the types of nicotinic cholinergic receptors?

A

Ionotropic Nicotinic receptors:

  1. muscle receptors: NMJ. Antagonist= curare (paralysis)
  2. Neuronal receptors: pre and post synaptically. autonomic ganglia and common brain receptors
43
Q

Describe the histaminergic system

A 
Diffuse and widespread
arousal and attention 
reactivity of vestibular system 
mediation of allergic response 
influence of brain blood flow 
3 GPCR receptors

202- Theme 1 (10 decks)

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