PED1003/L17 Drugs of Abuse

Question 1

Give 3 examples of commonly abused drugs.

Answer 1

Nicotine
Opiates
Alcohol
Cannabis
Cocaine
Amphetamines
Ketamine

Question 2

Why do people continue to abuse drugs? (2)

Answer 2

Satisfy cravings (psychological withdrawal)
Avoid unpleasant physical sensations (physical withdrawal)

Question 3

Describe the reward pathway. (5)

Answer 3

DA neurones with cell bodies in VTA project to n. accumbens (ventral striatum)
Activation of neurones releases DA
Acts on inhibitory D2 receptors
Inhibits n. accumbens neurones
Elicits reward pathway

Question 4

What is the primary target of amphetamines?

Answer 4

Plasma membrane transporters

Question 5

Which amphetamine has affinity for DAT and NAT?

Answer 5

d-Amphetamine

Question 6

Which amphetamine has highest affinity for DAT?

Answer 6

Metamphetamine

Question 7

Which amphetamine has affinity for DAT, NAT and SERT?

Answer 7

Ecstasy

Question 8

What occurs when amphetamines enter the neurone? (5)

Answer 8

Amphetamine enters nerve terminal via plasma membrane transporter
Transported into vesicles by VMAT2
Release of stored neurotransmitter into cytosol
Membrane transporter reverses to release NTM into synaptic cleft
Reuptake of released NTM blocked

Question 9

What symptoms are caused by DA transporters? (3)

Answer 9

High impulsivity
Psychosis
Stereotyped behaviours

Question 10

What symptoms are caused by NA transporters? (2)

Answer 10

Locomotor activation
Alertness

Question 11

What symptoms are caused by the 5-HT transporter? (2)

Answer 11

Empathogenic
Anorectic

Question 12

Explain briefly how amphetamines activate the reward pathway. (2)

Answer 12

Increase DA release and increase stimulation of D2 receptors in n. accumbens
DA neurones inhibit n. accumbens neurones

Question 13

Describe the psychological and physical dependence of amphetamines. (2)

Answer 13

Cause psychological dependence (craving)
No physical dependence or withdrawal

Question 14

What is the mechanism by which cocaine works?

Answer 14

Blocks DA transporter

Question 15

Describe the mechanism of action of cocaine. (3)

Answer 15

Binds to DAT plasma membrane transporter
Reuptake of released DA blocked
Level/duration of DA in synaptic cleft increased

Question 16

Give 3 exogenous opioids.

Answer 16

Codeine
Pethidine
Morphine
Diamorphine (heroin)
Fentanyl

Question 17

Give 3 endogenous opioids.

Answer 17

Enkephalins
Dynorphins
B-endorphin

Question 18

How do opioids act?

Answer 18

Through G-protein coupled receptors

Question 19

What do mew receptors in n. accumbens (ventral striatum) mediate?

Answer 19

Euphoria

Question 20

What do mew receptors in spinal cord mediate?

Answer 20

Analgesia

Question 21

What do mew receptors in the gut mediate?

Answer 21

Reduced motility

Question 22

What do mew receptors in the brainstem mediate?

Answer 22

Respiratory depression

Question 23

What do the effects of opioids depend on? (2)

Answer 23

Relative affinity for mew, delta and kappa receptors
Route of administration into CNS

Question 24

Define tolerance and explain why it occurs.

Answer 24

A state in which response to given concentration of drug is reduced
Due to receptor adaptation - down regulation of mew receptors

Question 25

Explain how opioids activate the reward pathway. (3)

Answer 25

Activate mew receptors decrease GABA release DA neurones are desinhibited and fire more AP INhibit n. accumbens neurones directly

Question 26

How can the effects of opioids be reversed?

Answer 26

Mew receptor antagonists E.g., naloxone

Question 27

What kind of drug is ketamine?

Answer 27

NMDA receptor antagonist

Question 28

What are the effects of glutamate mediated by? (2)

Answer 28

Excitatory ligand gated ion channel receptors G-protein linked receptors

Question 29

Describe the structure of the glutamate NMDA receptor.

Answer 29

Tetrameric structure Dimers of GluN1 and GluN2(A-D), GluN3

Question 29

How does ketamine activate the reward pathway?

Answer 29

Blocks NMDA receptors Reduces firing of n. accumbens neurones

Question 30

What kind of drug is nicotine?

Answer 30

ACh receptor (nAChR) agonist

Question 31

Give 3 cholinergic systems in the brain.

Answer 31

Medial septal n. Diagonal band of Broca N. Basalis Meynert Laterodorsal tegmentum Pedunculopontine tegmentum

Question 32

What kind of receptor are nicotinic receptors? (2)

Answer 32

Ligand-gated ion channel receptors Pentameric

Question 33

Which nicotinic receptors are responsible for reinforcing effects of nicotine? (3)

Answer 33

A4B2 A6B2 Both on DA cell bodies of VTA

Question 34

How does nicotine activate the reward pathway?

Answer 34

Activates DA neurones directly and indirectly via Glu inputs

Question 35

Describe the psychological and physical dependence of nicotine. (2)

Answer 35

Can cause psychological dependence (cravings) Does not cause physical dependence

Question 36

What is cannabis converted into in the body?

Answer 36

From Delta(9)THC to 11-hydroxyTHC

Question 37

Which receptors does cannabis interact with in the body?

Answer 37

G-protein coupled receptors CB1 and CB2

Question 38

What is the endogenous agonist ligand (endocannabinoid) of cannabinoid receptors?

Answer 38

Anandamide

Question 39

How do cannanbinoids cause retrogade signalling? (3)

Answer 39

Released neurotransmitter activates receptor on postsynaptic neurone Cannabinoid released and CB1 on presynaptic neurone activated Neurotransmitter release from presynaptic neurone reduced

Question 40

Name 2 non-rewarding addictive substances.

Answer 40

Codeine Benzodiazepines

Question 41

Give 3 features of benzodiazepines.

Answer 41

Sedative Hypnotic Anxiolytic Anticonvulsant Muscle relaxant

Question 42

Describe the action of the GABA(A) receptor complex and the effect of BDZs. (3)

Answer 42

Pentamer chloride channel Allosteric change opens Cl- channel BDZs enhance GABA(A) function