CB L1 - Drug addiction

Question 1

Define reinforcing

Answer 1

when an animal will perform a behavior in order to obtain that stimulus

(objective)

Question 2

What is rewarding?

Answer 2

Reward is linked to euphoria: a feeling of great happinesss or well-being

(subjecting)

Question 3

Rewarding substances can lead to…

Answer 3

addiction

Question 4

What pathway leads to addition?

Where does it start? end? What neurotransmitter?

Answer 4

Mesolimbic pathway
Cell bodies in the venteral tegmental area

leading to the nucleus accumbens

DA

Question 5

All drugs of abuse show the release of DA where in the brain

Answer 5

nucleus accumbens

Question 6

What sort of behavior releases DA - natural rewards?

Answer 6

Food and sex

Question 7

Substance that causes dysphoria?

Answer 7

u-50,488 (kappa agonist)

shows a reduction in DA release

Question 8

Do psychoactive substances release DA?

Answer 8

No DA release with TCAs and antipsychotics - therefore its not psychoactive that causes DA release

Question 9

What is the VTA?

NAcc?

Answer 9

venteral tegmental area

Neucleus accumbans

Question 10

What connects to the DA neurone in the VTA?

Answer 10

GABA neurone (inhibitory)

Question 11

Where do cocaine and amphetamine act?

Answer 11

inhibit DA reuptake in the NAcc

Question 12

Where do optiates and cannabis act?

Answer 12

inbihit the GAVEergic interneurone in the VTA.

less inbihibition to DA neurone

Question 13

Where do ethanol and nicotine act?

Answer 13

Directing activate the DA neuron (that leads from the VTA to the NAcc)

Question 14

3 types of ‘dependence’

Answer 14

• Physical dependence (withdrawal)
• Negative reinforcement (alleviation of underlying problems)
• Positive reinforcement (psychological dependence)

Question 15

What proportion of users become addicts?

Answer 15

Only a small proportion

Question 16

4 features of psychological dependannce

Answer 16

-extremely high motivation to take drugs with activities focused on procurement and consumption

• difficulty stopping/limiting drug use
• use continued despite harmful consequences
• high propensity to relapse after cessation of use

Question 17

4 features of psychological dependannce

Answer 17

-extremely high motivation to take drugs with activities focused on procurement and consumption

• difficulty stopping/limiting drug use
• use continued despite harmful consequences
• high propensity to relapse

Question 18

3 major stimuli for human relapse

Answer 18

taking a small dose of the drug
stress
being presented with cues associated with drug taking

Question 19

What % of recovering addicts will relapse within 1 year

Answer 19

70-80%

Question 20

What is the animal version of relapse

Answer 20

reinstatement

Question 21

2 methods to assess rewarding effects of drugs in animals

Answer 21

self-administration

conditional place preferance

Question 22

Self-administration is

Answer 22

animals is trained so that when a lever comes out and they press it they get an injection of drug directly into the brain

Question 23

2 exceptions of drugs that don’t release DA?

will rats administer them?

Answer 23

• Diazepam (rats self admin - for anxiety relief?)

- LSD (rats won’t self administer - different drives to take this: dissociation not euphoria)

Question 24

conditional place preference is…

Answer 24

Inject animal with drug or saline and place in compartment after.On test day animal receives no injection and separating door is removed.

Rewarding drugs increase time spent in the drug related environment.

Question 25

conditional place preference is…

Answer 25

Inject animal with drug or saline and place in compartment after.On test day animal receives no injection and separating door is removed.

Rewarding drugs increase time spent in the drug related environment.

Question 26

How do we reinstate a behaviour in an animal

Answer 26

1. Pressing lever for cocaine
2. ‘Extinction’ - pressing lever does not release cocaine (not the same as fogetting or reinstatement wouldn’t work)
3. ‘Drug-primed reinstatement’ - after cocaine injection they press the lever more than ever - motivation has changed

(works with stress and cues too)

Question 27

D2 receptor family includes: …………..and is …………….. coupled

Answer 27

D2, D3, D4

Gi/o coupled

Question 28

D1 receptor family includes: …………..and is …………….. coupled

Answer 28

D1 & D5

Gs-coupled

Question 29

the DA neurones reaching the NA connect to…..

which have what type of receptors

Answer 29

medium spiny neurones

D1 or D2 family: they have opposing effects so why activate both? - probably project to different brain regions.

Question 30

Where do D2 medium spiny neurones lead to?

Answer 30

The frontal cortex- probably enable us to feel euphoria

Question 31

Where do D1 medium spiny neurones lead?

Answer 31

Feedback loop to the VTA (they are GABAergic)

Question 32

Negative affect hypothesis

Answer 32

Eventually you start to be dysphoric and you need the drugs to get back to baseline.

So the motivation to take drug has changed, you need it to feel normal

Question 33

Negative affect hypothesis

Answer 33

Eventually you start to be dysphoric and you need the drugs to get back to baseline.

So the motivation to take drug has changed, you need it to feel normal

Question 34

Repeated withdrawl affets baseline mood and may lead to relapse - two theories accounting for this?

Answer 34

Dysregulation of stress hormones

Increased production of dynorphin

Question 35

What is dynorphin

Answer 35

endogenous ligand for kappa opioid receptor.

Kappa receptor activation inhibits DA neurone

Consequently decrease in basal DA levels

Question 36

How does DA cause an increase in dynorphin?

Answer 36

D1 receptors activate adenyl cyclase, increases CREB. CREB is TF which enhances transcription of dynorphin.

Even after stimulus the TF and protein stick around, long term effects