T1 L10: How do drugs control the brain?

Question 1

What are the effects of too much GABA?

Answer 1

Loss of consciousness and coma

Question 2

What are the effects of too little GABA?

Answer 2

Convulsions and seizures

Question 3

What are the 2 main neuronal types?

Answer 3

Projection neurons and local interneurons

Question 4

Describe the properties of GABA (A) ionotropic receptors

Answer 4

• Ligand gated Cl- channel

- Fast IPSP’s

Question 5

Describe the properties of GABA (B) metabotropic receptors

Answer 5

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

Question 6

Describe the structure of GABA (A) receptors

Answer 6

Heteropentameric structure
(2-alpha + 3 more subunits)

Question 7

Describe the structure of GABA (B) receptors

Answer 7

Complex receptor with multiple binding sites

Question 8

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

Answer 8

Muscimol (agonist)

Bicuclline (antagonist)

Question 9

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

Answer 9

Benzodiazapine
Barbiturates
Alcohol

Question 10

What effect does Benzodiazepine have on GABA (A)?

Answer 10

• 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

Question 11

What effect do Barbiturates have on GABA (A)?

Answer 11

They increase duration of channel openings.

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

Question 12

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

Answer 12

On the alpha subunit

Question 13

How does Benzodiazepine indirectly agonise GABA (A) receptors?

Answer 13

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

Question 14

What are the effects of Benzodiazapine?

Answer 14

Reduce anxiety
Cause sedation
Reduce convulsions
Relax muscles
Cause amnesia

Question 15

Which receptors does alcohol interact with?

Answer 15

GABA (A)
NMDA
glycine
nicotinic
serotonin

Question 16

Which type of GABA receptor does Baclofen agonise?

Answer 16

GABA (B)

Question 17

What is Baclofen used for?

Answer 17

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

Question 18

When can GABA be excitatory?

Answer 18

If the Cl- electrochemical gradient allows this during development

Question 19

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

Answer 19

It inhibits adenylyl cyclase

Question 20

Where is dopamine produced?

Answer 20

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

Question 21

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

Answer 21

D1

Question 22

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

Answer 22

It stimulates adenylyl cyclase - cAMP - PKA

Question 23

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

Answer 23

D2

Question 24

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

Answer 24

Parkinson’s

Question 25

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

Answer 25

Huntington's

Question 26

What is the mesolimbic system?

Answer 26

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

Question 27

What are some immediate effects of psychomotor stimulants?

Answer 27

- 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

Question 28

Give examples of psychomotor stimulants

Answer 28

Cocaine, Amphetamine

Question 29

What is Stereotypy?

Answer 29

Repetitive movements or sounds

Question 30

What are some long-term effects of psychomotor stimulants?

Answer 30

-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

Question 31

What is the Mesocortical system?

Answer 31

A dopaminergic system that connects the Central Tegmental area (VTA) to the prefrontal cortex Functions as part of the working memory and planning

Question 32

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

Answer 32

Schizophrenia

Question 33

Where in the brain is Serotonin produced?

Answer 33

In the Raphe nucleus

Question 34

What is the serotonergic system involved in?

Answer 34

Mood, sleep, pain, emotion, appetite

Question 35

What type of drug is Fluoxetine (Prozac)?

Answer 35

An SSRI

Question 36

What effect does MNDA have on serotonin?

Answer 36

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

Question 37

What effect does LSD have on Serotonin?

Answer 37

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

Question 38

What is the Noradrenergic system?

Answer 38

A neuronal system that is responsible for the synthesis, storage, and release of the neurotransmitter norepinephrine It has a role in arousal and attention

Question 39

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

Answer 39

Gq

Question 40

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

Answer 40

Gi

Question 41

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

Answer 41

Gs

Question 42

Where is the adrenergic system of the brain located?

Answer 42

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

Question 43

Where is the cholinergic system of the brain located?

Answer 43

In the basal forebrain complex

Question 44

What is Myasthenia gravis in terms of the cholinergic system?

Answer 44

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

Question 45

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

Answer 45

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

Question 46

Which system is a Nicotine addiction associated with?

Answer 46

The cholinergic system

Question 47

What causes Epilespy?

Answer 47

Caused by mutations in the nicotinic receptor genes.

Question 48

What are Acetylcholinesterase's inhibitors used to treat?

Answer 48

Alzheimer's and Myasthenia gravis

Question 49

How does Botox work?

Answer 49

It prevents release of ACh at the NMJ

Question 50

How does Latrotoxin work?

Answer 50

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

Question 51

What are the 2 types of ACh receptor?

Answer 51

Muscarinic - Metabotropic | Nicotinic - Ionotropic

Question 52

What is curare?

Answer 52

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

Question 53

Describe the structure of nicotinic receptors

Answer 53

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

Question 54

Where is the Histaminergic system found in the brain?

Answer 54

The Tuberomammillary nucleus of the hypothalamus

Question 55

What is the Histaminergic system for?

Answer 55

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