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2.1 T1: Fundamental Neuroscience and the Brain > T1 L10: How do drugs control the brain? > Flashcards

T1 L10: How do drugs control the brain? Flashcards

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1
Q

What are the effects of too much GABA?

A

Loss of consciousness and coma

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2
Q

What are the effects of too little GABA?

A

Convulsions and seizures

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3
Q

What are the 2 main neuronal types?

A

Projection neurons and local interneurons

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4
Q

Describe the properties of GABA (A) ionotropic receptors

A
  • Ligand gated Cl- channel

- Fast IPSP’s

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5
Q

Describe the properties of GABA (B) metabotropic receptors

A
  • G-protein coupled receptors
  • Indirectly coupled to K+ or Ca2+ channels through 2nd messengers
  • Slow IPSP’s
  • Both pre- and post-synaptic
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6
Q

Describe the structure of GABA (A) receptors

A 
Heteropentameric structure
(2-alpha + 3 more subunits)
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7
Q

Describe the structure of GABA (B) receptors

A

Complex receptor with multiple binding sites

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8
Q

What are some direct agonists and antagonists of GABA (A) receptors?

A

Muscimol (agonist)

Bicuclline (antagonist)

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9
Q

What are some indirect agonists of GABA (A) receptors?

A

Benzodiazapine
Barbiturates
Alcohol

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10
Q

What effect does Benzodiazepine have on GABA (A)?

A
  • It increases the receptor affinity for GABA
  • Increases frequency of channel opening
  • Anxiolytic and hypnotic effects in the short term, less satisfactory in the long term

Can be addictive

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11
Q

What effect do Barbiturates have on GABA (A)?

A

They increase duration of channel openings.

This is why they can be used for anaesthesia and epilepsy treatment

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12
Q

Where on the GABA (A) receptor does Benzodiazepine bind?

A

On the alpha subunit

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13
Q

How does Benzodiazepine indirectly agonise GABA (A) receptors?

A

It binds to the alpha subunit, changes conformation of the receptor so GABA activation of the receptor is more effective

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14
Q

What are the effects of Benzodiazapine?

A 
Reduce anxiety
Cause sedation
Reduce convulsions
Relax muscles
Cause amnesia
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15
Q

Which receptors does alcohol interact with?

A 
GABA (A)
NMDA
glycine
nicotinic
serotonin
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16
Q

Which type of GABA receptor does Baclofen agonise?

A

GABA (B)

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17
Q

What is Baclofen used for?

A

Used as a muscle relaxant to reduce spasticity Eg, Huntington’s disease

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18
Q

When can GABA be excitatory?

A

If the Cl- electrochemical gradient allows this during development

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19
Q

What does the Gi part of a G-protein do?

A

It inhibits adenylyl cyclase

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20
Q

Where is dopamine produced?

A

In the substantia nigra and the ventral tegmental area of the midbrain

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21
Q

Which dopamine receptor is found on the Gs part of a G-protein?

A

D1

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22
Q

What does the Gs part of a G-protein do?

A

It stimulates adenylyl cyclase - cAMP - PKA

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23
Q

Which dopamine receptor is found on the Gi part of a G-protein?

A

D2

24
Q

Which disease is caused by destruction of DA projections from the SN to the basal ganglia?

A

Parkinson’s

25
Q

Which disease is caused by destruction of DA target neurones in the stratum?

A

Huntington’s

26
Q

What is the mesolimbic system?

A

The reward pathway, is a dopaminergic pathway in the brain.

Cell bodies from the ventral tegmental area (VTA) project to the nucleus accumbens in the limbic system

27
Q

What are some immediate effects of psychomotor stimulants?

A
  • Feeling of increased alertness and self confidence
  • decreased appetite
  • Euphoria
  • Large doses can cause stereotypy and psychosis
  • Increased heart rate, increased blood pressure, dilated pupils
28
Q

Give examples of psychomotor stimulants

A

Cocaine, Amphetamine

29
Q

What is Stereotypy?

A

Repetitive movements or sounds

30
Q

What are some long-term effects of psychomotor stimulants?

A

-Natural rewards increase DA transmission and lead to reinforcement of associated behaviours
They cause increased DA so taking drugs is reinforced
-Downregulation of endogenous DA causes craving

31
Q

What is the Mesocortical system?

A

A dopaminergic system that connects the Central Tegmental area (VTA) to the prefrontal cortex

Functions as part of the working memory and planning

32
Q

Which disease is caused by dysfunction of the Mesocortical dopaminergic system?

A

Schizophrenia

33
Q

Where in the brain is Serotonin produced?

A

In the Raphe nucleus

34
Q

What is the serotonergic system involved in?

A

Mood, sleep, pain, emotion, appetite

35
Q

What type of drug is Fluoxetine (Prozac)?

A

An SSRI

36
Q

What effect does MNDA have on serotonin?

A

Causes serotonin transporters to run in reverse so there is increased release and reduced reuptake of serotonin

37
Q

What effect does LSD have on Serotonin?

A

It’s a potent agonist of 5HT1A receptors in the raphe nucleus.
It causes a dreamlike state with altered sensory perceptions

38
Q

What is the Noradrenergic system?

A

A neuronal system that is responsible for the synthesis, storage, and release of the neurotransmitter norepinephrine

It has a role in arousal and attention

39
Q

Which G-protein part do alpha-1 adrenergic receptors interact with?

A

Gq

40
Q

Which G-protein part do alpha-2 adrenergic receptors interact with?

A

Gi

41
Q

Which G-protein part do beta-1, 2, and 3 adrenergic receptors interact with?

A

Gs

42
Q

Where is the adrenergic system of the brain located?

A

Primarily in the lateral tegmental area, projecting to the thalamus and hypothalamus

43
Q

Where is the cholinergic system of the brain located?

A

In the basal forebrain complex

44
Q

What is Myasthenia gravis in terms of the cholinergic system?

A

A peripheral disorder of the cholinergic system. It an autoimmune disease that causes destruction of cholinergic receptors in the muscles (weak NMJ’s)

Symptoms: Muscle weakness, eventual moss of muscle activity

45
Q

What is Alzheimer’s disease in terms of the cholinergic system?

A

A brain disorder of the cholinergic system causing loss of cholinergic neurones in the basal ganglia

46
Q

Which system is a Nicotine addiction associated with?

A

The cholinergic system

47
Q

What causes Epilespy?

A

Caused by mutations in the nicotinic receptor genes.

48
Q

What are Acetylcholinesterase’s inhibitors used to treat?

A

Alzheimer’s and Myasthenia gravis

49
Q

How does Botox work?

A

It prevents release of ACh at the NMJ

50
Q

How does Latrotoxin work?

A

It causes permanent release of ACH so there is depletion of ACh at the NMJ

51
Q

What are the 2 types of ACh receptor?

A

Muscarinic - Metabotropic

Nicotinic - Ionotropic

52
Q

What is curare?

A

a bitter resinous substance obtained from the bark and stems of some South American plants used to cause muscle paralysis

It antagonises nicotinic receptors

53
Q

Describe the structure of nicotinic receptors

A

Heterometric combination of alpha-3,4,5 and beta-2,3,4,6
Homomeric receptors: alpha-7, 8, 9

alpha-3 beta-4 on autonomic ganglia
alpha-4 beta-2 and alpha-7 most common brain receptors

54
Q

Where is the Histaminergic system found in the brain?

A

The Tuberomammillary nucleus of the hypothalamus

55
Q

What is the Histaminergic system for?

A
  • Arousal and attention
  • Reactivity of vestibular system
  • Mediation of allergic responses
  • Influence of brain blood flow

2.1 T1: Fundamental Neuroscience and the Brain (24 decks)

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