L19 - Addiction Flashcards
> x/10 deaths from addiction, x% of this is alcohol and tobacco
1, 90
Effect opiates have on DA neuron?
Disinhibit it
Basolateral amygdala important in association of
Cue salience
Define addiction
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)
Difference between use, escalation and loss of control prone drug users?
Use prone - everything relatively “normal”
Escalation prone - drug use takes over recreational time
Loss of control prone - totally preoccupied with obtaining and using drugs
In addicted state, how is PFC regulation of accumbal outflow affected?
It is diminished so it cannot control basal ganglia outflow in addicted individual so they can’t make good decisions
Abstinence vs relapse circuit
Relapse circuit
-Prelimbic cortex to NAc core
Abstinence/extinction circuit
-Infralimbic cortex to Nac shell
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?
Hypo - there is also impaired LTD
Addict and non-addict animals using drugs have impaired LTD. How is the recovery different for these two types of animals?
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.
What type of receptor (GABA/Glycine/Glutamate/Ach/DA/5-HT)is on the synapse between prelimbic cortex and nucleus accumbens?
Glutamatergic
Glutamate release is regulated by _____ on the presynaptic terminal? -ve or +ve feedback? Regulated by ____ on postsynaptic terminal? These are linked to?
MGlu2/3 autoreceptors - -ve feedback
MGlu5 - linked to NMDA R (important for synaptic grading and postsynaptic plasticity)
Glu levels in extracellular space are regulated by transporters in astrocyte called?
GLT1 aka EAAT2 takes Glu out
AND
Xc- is putting Glu into extracellular space
In drug withdrawal condition, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?
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
In relapse, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?
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
How can we reverse the altered glutamate homeostasis in addiction?
N-Acetylcysteine mechanism - also makes rats less prone to relapse
In social drinkers, what brain areas are activated? What about heavy drinkers?
VS and PFC
Heavy drinkers - shifts from VS to Rostral Dorsal Striatum activation (much more involved in habits)
More than a ventral to dorsal shift in the striatum but within DS, there is a ____ to ____ shift as drug taking becomes habitual
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
Cue exposure therapy reduces alcohol cue-induced prefrontal and striatal activation compared to standard treatment. What is the problem with cue exposure therapy?
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)
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?
Inactive, extinction of context salience
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
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
What’s the difference between cue EXT for adults and adolescents?
Adolescents are less able to extinguish the salience of a drug related cue - making them more prone to relapse
What drug can rescue adolescent deficit in cue extinction?
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
