L19 - Addiction

Question 1

> x/10 deaths from addiction, x% of this is alcohol and tobacco

Answer 1

1, 90

Question 2

Effect opiates have on DA neuron?

Answer 2

Disinhibit it

Question 3

Basolateral amygdala important in association of

Answer 3

Cue salience

Question 4

Define addiction

Answer 4

Chronic relapsing disorder which consists of a compulsive pattern of drug-seeking and drug taking behaviour (take place at the expense of other activities and persists despite adverse consequences)

Question 5

Difference between use, escalation and loss of control prone drug users?

Answer 5

Use prone - everything relatively “normal”

Escalation prone - drug use takes over recreational time

Loss of control prone - totally preoccupied with obtaining and using drugs

Question 6

In addicted state, how is PFC regulation of accumbal outflow affected?

Answer 6

It is diminished so it cannot control basal ganglia outflow in addicted individual so they can’t make good decisions

Question 7

Abstinence vs relapse circuit

Answer 7

Relapse circuit
-Prelimbic cortex to NAc core

Abstinence/extinction circuit
-Infralimbic cortex to Nac shell

Question 8

In addict-like rats who are resistant to punishment, their prelimbic cortex neurons are hypo/hyperactive. How is LTD (mGluR2/3 dependent synaptic plasticity) affected?

Answer 8

Hypo - there is also impaired LTD

Question 9

Addict and non-addict animals using drugs have impaired LTD. How is the recovery different for these two types of animals?

Answer 9

As the use continues, in 2-3 months of drug use there is an endogenous recovery mechanism whereby in these non-addict rats, their LTD impairment recovers but addict like animals are still impaired. This suggests that this transition to addiction is related to some persistent corticostriatal dysfunction where for addiction prone people, that will not resolve and they will become addicted.

Question 10

What type of receptor (GABA/Glycine/Glutamate/Ach/DA/5-HT)is on the synapse between prelimbic cortex and nucleus accumbens?

Answer 10

Glutamatergic

Question 11

Glutamate release is regulated by _____ on the presynaptic terminal? -ve or +ve feedback? Regulated by ____ on postsynaptic terminal? These are linked to?

Answer 11

MGlu2/3 autoreceptors - -ve feedback

MGlu5 - linked to NMDA R (important for synaptic grading and postsynaptic plasticity)

Question 12

Glu levels in extracellular space are regulated by transporters in astrocyte called?

Answer 12

GLT1 aka EAAT2 takes Glu out
AND
Xc- is putting Glu into extracellular space

Question 13

In drug withdrawal condition, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?

Answer 13

Swelling of synaptic spine, increased amounts of AMPA R on post syaptic terminal, increased amount of Glu in extracellular space as EAAT2 and MGluR2/3 autoreceptors are impaired

Question 14

In relapse, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?

Answer 14

Huge glutamate release, swelling of post synaptic spine, since there is impairment on EAAT2 and MGLuR2/3, there is hyper activity on post synaptic cell

Question 15

How can we reverse the altered glutamate homeostasis in addiction?

Answer 15

N-Acetylcysteine mechanism - also makes rats less prone to relapse

Question 16

In social drinkers, what brain areas are activated? What about heavy drinkers?

Answer 16

VS and PFC

Heavy drinkers - shifts from VS to Rostral Dorsal Striatum activation (much more involved in habits)

Question 17

More than a ventral to dorsal shift in the striatum but within DS, there is a ____ to ____ shift as drug taking becomes habitual

Answer 17

Medial to lateral

• Medial is goal orientated so when rat is punished, it stops taking cocaine
• Lateral are habitually responding, becoming insensitive to punishment as behaviour is more automatic

Question 18

Cue exposure therapy reduces alcohol cue-induced prefrontal and striatal activation compared to standard treatment. What is the problem with cue exposure therapy?

Answer 18

It is context dependent - it needs to be performed in a relevant context. E.g. develop a mock bar rather than doing therapy in a sterile office
*Relies on extinction/inhibitory/ learning (abstinence circuit)

Question 19

Re-exposure to the drug-taking context leads to a “protection” against cocaine-primed reinstatement - this has a better effect with an active or inactive lever? What else do you also need to treat addiction?

Answer 19

Inactive, extinction of context salience

Question 20

Post session MTEP (mGlu5 antag) impairs extinction of contextual salience, suggests mGlu5 signalling involved in the integration of contextual salience - when we block mGlu5, relapse is exacerbated

Answer 20

Post session MTEP (mGlu5 antag) impairs extinction of contextual salience, suggests mGlu5 signalling involved in the integration of contextual salience - when we block mGlu5, relapse is exacerbated

Question 21

What’s the difference between cue EXT for adults and adolescents?

Answer 21

Adolescents are less able to extinguish the salience of a drug related cue - making them more prone to relapse

Question 22

What drug can rescue adolescent deficit in cue extinction?

Answer 22

Quinpirole - DA D2R agonist in the Infralimbic cortex

Aripiprazole (partial agonist) can also be used

*D2 signalling in infralimbic cortex (extinction pathway) increases extinction learning -protecting rats from relapse