M101C Lec 6

What are the core characteristics of addiction?

Compulsion to seek and take the drug despite negative consequences with cravings loss of control and negative emotional state when drug is unavailable

Why is addiction considered a relapsing condition?

Individuals remain vulnerable to relapse even after long periods of abstinence

What triggers relapse in addiction?

Stress emotional changes drug associated cues and people places and things linked to drug use

What does the allostasis theory propose about addiction?

Chronic drug use creates a negative emotional state through homeostatic opponent processes

What happens to the reward system in allostasis theory?

It becomes overstimulated then counteracted by anti reward and stress systems

What are opponent B processes?

Decreased dopamine function and increased CRF stress signaling

How does reinforcement shift in addiction?

From positive reinforcement feeling good to negative reinforcement avoiding feeling bad

What does ICSS measure in addiction studies?

The brain stimulation reward threshold reflecting reward system sensitivity

What does an increased ICSS threshold indicate?

Reduced reward sensitivity and a negative emotional state

What behavioral pattern supports allostasis theory?

Long access drug use leads to escalation and increased reward thresholds

What happens in alcohol vapor dependence models?

Withdrawal increases reward thresholds and leads to escalated intake

What is hypodopamine function?

Reduced dopamine activity during withdrawal linked to drug seeking

Where is CRF elevated during withdrawal?

In the extended amygdala and BNST

What happens when CRF receptors are blocked?

Reduced negative emotional state and reduced drug seeking escalation

Why is CRF a therapeutic target?

It mediates stress and negative emotional states during withdrawal

What other stress system is being explored besides CRF?

Dynorphin kappa opioid system

How can dopamine normalization help addiction?

It may reduce dysphoria and decrease drug seeking

How do opioid replacement therapies help?

They prevent strong withdrawal effects and stabilize emotional state

What are strengths of allostasis theory?

Explains withdrawal negative affect escalation and identifies therapeutic targets

What is a limitation of allostasis theory?

Does not explain cue triggered relapse or long term craving increases

What does incentive sensitization theory explain?

Why drug cues become powerful motivators and drive craving

What is liking?

The pleasurable emotional experience of a reward

What is wanting?

The motivational drive to obtain a reward or respond to cues

How are liking and wanting related?

They usually align but can become dissociated

What role does dopamine play in wanting?

It regulates motivation and response to reward predictive cues

Does dopamine affect liking?

No it primarily affects wanting not pleasure

What vulnerability does dopamine create in addiction?

Wanting can increase even if liking decreases

What happens to drug associated cues over time?

They gain excessive motivational salience

What is sensitization in addiction?

Increased responsiveness of dopamine systems to drug cues

What happens to pleasure over time with drug use?

It often decreases or stays the same

What happens to wanting over time?

It increases especially in response to cues

What is the core idea of incentive sensitization theory?

Chronic drug use sensitizes dopamine systems causing excessive wanting

Do all addictive drugs affect dopamine?

Yes directly or indirectly they increase dopamine

How does cocaine affect dopamine?

Blocks reuptake increasing dopamine in synapse

How do amphetamines affect dopamine?

Cause release of dopamine from vesicles

How do opioids increase dopamine?

Disinhibit dopamine neurons via mu opioid receptors

What happens to dopamine response after repeated drug use?

It becomes sensitized and more reactive to cues

What is PIT used to measure?

Cue triggered reward wanting

What happens to PIT after psychostimulant exposure?

It increases showing enhanced wanting

What do cocaine cues do in PIT tasks?

Increase drug seeking and taking behavior

How do alcohol cues affect behavior?

They strongly increase alcohol seeking

How do drug cues influence human choice?

They bias behavior toward drug rewards

What do AUD patients show in PIT tasks?

Greater sensitivity to reward predictive cues

What is sign tracking?

Approaching and interacting with a reward predictive cue

What is goal tracking?

Ignoring the cue and going directly to the reward location

What do sign trackers represent?

High attribution of motivational value to cues

What do goal trackers represent?

Use cues as information not motivation

How do sign trackers differ in addiction models?

They show stronger drug seeking and relapse behavior

What happens in cue induced reinstatement?

Sign trackers show strong relapse while goal trackers show weak response

What is drug primed reinstatement?

A small drug dose triggers relapse behavior

How do sign trackers respond to drug priming?

They relapse strongly

What pattern is seen in nicotine studies?

Sign trackers show more intake and stronger relapse

What influences sign tracking tendencies?

Genetics experience and prior drug exposure

What effect does adolescent alcohol exposure have?

Increases likelihood of becoming a sign tracker

What is incubation of craving?

Increase in cue triggered drug seeking over time after abstinence

How does craving change over time?

It increases and peaks weeks to months later

What does incubation of craving explain?

Persistent relapse risk after long abstinence

What happens at 45 days vs 1 day withdrawal?

Cue induced relapse is much stronger at 45 days

How long can incubation effects last?

Hundreds of days in animal models

What brain pathway is central to cue wanting?

VTA to nucleus accumbens core dopamine pathway

What happens when NAc core is inactivated?

Cue induced drug seeking is reduced

What is the role of D1 receptors?

They mediate dopamine driven motivational effects

What happens when D1 receptors are blocked?

Cue induced reinstatement decreases

How does cocaine history affect dopamine?

Increases cue evoked dopamine release

What predicts craving in humans?

Greater cue evoked dopamine release

What is special about sign trackers and dopamine?

Their behavior is highly dopamine dependent

What happens when dopamine is increased in sign trackers?

Cue driven drug seeking increases

What happens when dopamine is blocked in sign trackers?

Cue driven seeking decreases

What happens to dopamine after adolescent alcohol exposure?

Cue evoked dopamine increases

What predicts relapse in humans with AUD?

Higher NAc activation to cues

What are CP AMPARs?

Calcium permeable AMPA receptors inserted into synapses

When do CP AMPARs increase?

After long withdrawal periods around 35 to 60 days

What effect do CP AMPARs have?

Increase neuronal excitability and plasticity

What happens if CP AMPARs are blocked?

Late stage cue induced relapse is prevented

What does CP AMPAR insertion explain?

Incubation of craving over time

What is a key strength of incentive sensitization theory?

Explains cue driven relapse and craving

How does the theory explain craving vs pleasure?

Wanting increases while liking decreases

What individual differences does it explain?

Variation in vulnerability to addiction

What evidence supports the theory?

Animal studies human imaging PIT and dopamine data

What neural substrate is central in this theory?

Dopamine in nucleus accumbens core

How does it complement allostasis theory?

Adds explanation for cue driven craving and relapse

What is a limitation of incentive sensitization theory?

Does not fully explain stress induced relapse

What behavior is not well explained by the theory?

Compulsive drug use despite punishment

What is another limitation?

Heavy focus on dopamine may ignore other systems

What does allostasis emphasize?

Negative reinforcement and stress

What does incentive sensitization emphasize?

Cue driven craving and wanting

What are two pathways to addiction?

Avoidance via allostasis and craving via sensitization

What does hypo dopamine relate to?

Withdrawal and negative affect

What does hyper dopamine relate to?

Cue driven craving and motivation

Why is addiction complex?

Different drugs individuals and stages involve different mechanisms