Chris Bailey Lectures

Question 1

What does it mean to say a stimulus is reinforcing?

Answer 1

Something is reinforcing when an animal will perform a behaviour in order to obtain that stimulus. i.e. it is rewarding.

Question 2

What is physiological dependence?

Answer 2

Cravings, compulsive drug use, loss of control, addiction.

Question 3

What is physical dependence?

Answer 3

This is when stopping a drug causes a withdrawal syndrome. For example, the SSRI fluoxetine causes physical withdrawal symptoms if stopped abruptly but it is not addictive.

Question 4

What are the two concentrations of dopaminergic neurons in the brain?

Answer 4

Ventral tegmental area -> frontal cortex + nuclues accumbens.

Substantia nigra –> Caudate (parkinsons)

Question 5

What is the mesolimbic pathway?

Answer 5

This is the reward pathway, VTA –> nucleus accumbens.

Question 6

What impact does ethanol have on dopamine release?

Answer 6

Increases it.

Question 7

What impact does u-50 have on dopamine relase?

Answer 7

Decreases it. Disphoria.

Question 8

What impact do imipramine and haloperidol have on dopamine release?

Answer 8

no impact.

Question 9

How does cocaine increase dopamine levels?

Answer 9

Cocaine acts at the nerve terminal to inhibit the reuptake of dopamine from the synaptic cleft.

Question 10

How does amphetamine increase dopamine levels?

Answer 10

Amphetamine acts at the nerve terminal to inhibit reuptake of dopamine and also to cause dopamine release.

Question 11

How do opiates increase dopamine levels?

Answer 11

Opiates act on the mu-opioid receptors on GABAergic neurones.

This causes a disinhibition of DA neurones in VTA = more likely they will carry action potetial and release dopamine.

Question 12

How does activation of the mu-opioid receptor lead to disinhibition of DA neurones?

Answer 12

Mu-opioid receptor = Gi/o coupled.

Gi/o = inhibits AMP –> cAMP.

Gi/o = inhibits Ca2+ channels, preventing Ca2+ into cell.

Gi/o = activates K+ channels, increasing K+ efflux.

Question 13

How does ethanol increase dopamine levels?

Answer 13

Acts directly on DA neurones in VTA.

Decreases the AHP, increasing the firing rate = more dopamine relase.

Question 14

Mu-opioid Gi/o activation results in ______ of Ca2+ transport _____ DA neurones.

Answer 14

Mu-opioid Gi/o activation results in inhibition of Ca2+ transport into DA neurones.

Question 15

Mu-opioid Gi/o activation results in _________ K+ efflux from the DA neurone.

Answer 15

Increased, prevents hyperpolarisation?

Question 16

Opiates act on ______ receptors on ______ neurones to cause a disinhibition.

Answer 16

Opiates act on mu-opioid receptors on GABAergic neurones.

Question 17

Why does ethanol increase dopamine release?

Answer 17

It inhibits the potassium channels that are responsible for the after-hyperpolarisation, so the DA neurones are able to fire action potentials at a more rapid pace.

Question 18

Why does alcohol use inhibit memory formation?

Answer 18

NMDA receptor antagonist

Question 19

Why does alcohol impact balance?

Answer 19

Calcium channel antagonist.

Question 20

Ethanol has what effect on GABAa?

Answer 20

Allosteric modulator of GABAa.

Question 21

Why do people enjoy smoking? (pharmacologically)

Answer 21

Nicotine acts on nicotinic acetylcholine receptors on DA neurones in the VTA. This increases the firing rate and hence dopamine release and levels.

Question 22

How does THC cause stimulation of the reward pathway?

Answer 22

THC acts on cannabinoid receptors on GABAergic neurones. CB1.

Question 23

Why do sex and food stimulate the reward pathway?

Answer 23

Evolutionary approach to encourage behaviours which lead to propagation of genes.

Question 24

Which route of administration causes the fastest peak of drug concentration in the brain?

Answer 24

Inhalation, not injection.

Question 25

Which route of administration causes the slowest peak of drug concentration in the brain?

Answer 25

Ingestion.

Question 26

Which is the better (in terms of time to peak conc) route of administration of a drug, snorting or injection?

Answer 26

Injection. Order is: Inhalation > Injection > snorting/stuffing > ingestion.

Question 27

In terms of addiction, what is more important, the rate of dopamine release in the nucleus accumbens or the peak (total conc) attained from drug use?

Answer 27

The rate of dopamine release is more important, hence why injection and inhalation are associated with addiction.

Question 28

What is tolerance?

Answer 28

When continued use of a drug results in the need for increasing doses for equivalent effect.

Question 29

Which drugs of misuse does tolerance apply to most?

Answer 29

Opioids Ethanol Cannabinoids

Question 30

Why do people recently released from prison often die of overdose?

Answer 30

They have lost their tolerance during the time off drugs in prison. When they are released they attempt to take the same dose/amount and it is too much.

Question 31

What is the correlation between alcohol use and heroin overdose?

Answer 31

Heroin users often overdose with alcohol in their systems.

Question 32

Why do heroin users often overdose with alcohol in their systems?

Answer 32

Ethanol causes potential reversal of opioid tolerance and reversal of mu-opioid receptor desensitisation.

Question 33

Cardiac arrhythmias and psychosis are harms caused mostly by which drugs of abuse?

Answer 33

Psycho-stimulants.

Question 34

Infectious diseases result mostly from the use of what drugs and why?

Answer 34

Opiates - needles - blood sharing.

Question 35

How can alcohol withdrawal be treated pharmacologically? (3)

Answer 35

1. Benzodiazepines 2. Anti-epileptics 3. Antipsychotics

Question 36

How can opitate withdrawal be treated pharmacogically?

Answer 36

1. Clonidine - alpha agonist. 2. Benzodiazepeines 3. Sedation 4. Replacement therapy e.g. methadone, buprenorphine.

Question 37

How can nicotine withdrawal be treated?

Answer 37

Replacement therapy.

Question 38

Why is the relapse rate for drug addicts so high?

Answer 38

Replacement therapies do not solve the addication/psychological dependence issues. 80% relapse.

Question 39

What is varenicline?

Answer 39

Partial agonist of the nicotine receptors - provides partial relief.

Question 40

Why is it harder to overdose via buprenorphine than methadone?

Answer 40

Buprenorphine is only a partial agonist plus it is only administered via a patch or buccaly.

Question 41

What is aversion therapy for alcohol abuse based around?

Answer 41

The use of disulfiram.

Question 42

How does disulfiram work?

Answer 42

Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, which means many of the effects of a "hangover" are felt immediately after alcohol is consumed.

Question 43

What is a major problem relating to the use of naloxone/buprenorphine/naltrexone etc?

Answer 43

They prevent pain relief in event of injury.

Question 44

How is the issue of compliance regarding opioid antagonists being addressed?

Answer 44

Drug Depots in the skin - some drug users will dig these out however.

Question 45

What are the 3 major stimuli for relapse in humans?

Answer 45

1. Taking a small dose of the drug. 2. Stress 3. Being presented with a cue that reminds the person of drug taking - music, BBQ smell etc.

Question 46

In a drug user, how is the euphoric effect associated with a drug and the dysphoric effect of a comedown different to a drug niave person?

Answer 46

The euphoric effect becomes blunted - more drug for same effect. The dysphoric effect becomes exaggerated when not on drug/on comedown.

Question 47

What enzyme does disulfiram inhibit, what does this cause?

Answer 47

It inhibits acetaldehyde dehydrogenase = meaning effects of hangover are felt straight away.

Question 48

When a person is dependent on a drug, what can be said about the effect the drug has on their baseline level of happiness?

Answer 48

It simply returns it to a normal level - experienced by everyone else.

Question 49

How is it thought that repeated withdrawal affects baseline mood?

Answer 49

1. Dysregulation of stress hormones | 2. Increased production of dynorphin

Question 50

What is antalarmin?

Answer 50

Antalarmin is a non-peptide drug that blocks the CRF-1 receptor, and, as a consequence, reduces the release of ACTH in response to chronic stress.

Question 51

How does dynorphin result in reduced baseline happiness levels?

Answer 51

Dynorphins exert their effects primarily through the κ-opioid receptor (KOR), a G-protein-coupled receptor. Dynorphin decreases dopamine release by binding to KORs on dopamine nerve terminals.

Question 52

Why might kappa opioid receptor antagonists be a future drug treatment for addiction?

Answer 52

Dynorphin decreases dopamine release by binding to KORs on dopamine nerve terminals.

Question 53

What is the relationship between levels of D2 receptors and drug abuse?

Answer 53

Those with fewer receptors appear to use drugs more - rat studies.

Question 54

Recovered addicts have less of what type of receptor in the NAcc?

Answer 54

D2.

Question 55

Long term cocaine use in monkeys reduces the levels of what receptor in the accumbens?

Answer 55

D2.

Question 56

How does Buprion work?

Answer 56

Dopamine/noradrenaline reuptake inhibitor - may just work in addiction because it is an antidepressant.

Question 57

What is bromocriptine?

Answer 57

Partial D2 agonist.

Question 58

Addiction is what type of behaviour?

Answer 58

Learned.

Question 59

Why could inhibiting synaptic plasticity (and therefore memory formation) be useful in addiction treatment?

Answer 59

Memory formation is thought to occur because of synaptic plasticity, particularly at glutamatergic synapses. Inhibiting this = inhibits conditioned learning.

Question 60

How can interfering with memory formation be used to treat people who are already addicts?

Answer 60

By interfering with the process of reconsolidation.

Question 61

What is reconsolidation?

Answer 61

Reconsolidation is the process of strengthening memory.

Question 62

Why does disrupting reconsolidation extinguish memory?

Answer 62

Without the reconsolidation and synaptic plasticity memories are not reactivated and retained.

Question 63

Therapy that seeks to make addicts forget they are addicted would involve:

Answer 63

Re-exposure of addicts to cues related to their addiction. Use of agents that interfere with memory formation: propranolol.

Question 64

Current drug treatments are based around what? [4]

Answer 64

1. Replacement therapy. 2. Aversion therapy 3. Antagonists 4. Bupropion/Bromocriptine

Question 65

Future drug treatments for abuse are based around what? [4]

Answer 65

1. Antibodies 2. Stress hormone antagonists 3. Kappa opioid receptor antagonists 4. Agents that affect memory