5.2. Addiction: Theories of drug addiction

Factors influencing addiction vulnerability

1. Properties of drugs

2. Individual differences (genes/environment)• High impulsivity (D2 receptors)• History of stress (striatum, PFC)• Environmental enrichment

3. Drug-induced neuroadaptations• Enhanced drug motivation• Enhanced habit learning• Reduced behavioral inhibition

Drug use vs. addiction

Compulsive seeking of drugs?

Craving and relapse for drugs?

1. Properties of the drug

- Route of administration (speed of onset)

- Increased lipid solubility

Individual differences (genetic and environmental)

Genes

A large number of genes contribute to addiction vulnerability(risk) or addiction resilience (protection)

Environment

Environment (psychosocial factors) also plays an important role in neural and psychological development.

Gene X environment

Complex interactions between genes and environment.

2. Individual differences (2)

genetic/environmental

Increase addiction likelihood:

High impulsivity

•Genetic differences in dopamine D2 receptors increase vulnerability

A history of stress/trauma

• Enhanced habit learning – Striatum (DLS)

• Reduced behavioral inhibition – Prefrontal cortex

Decrease addiction likelihood:

Environmental enrichment (protective)

Impulsivity: Reduced D2 receptors

Reduced D2 receptor availability in striatum is correlated with impulsivity in meth abusers.

Impulsivity: Rats also show low D2 receptors in striatum

Similar effect in rats: high levels of premature (impulsive) responding show decreased D2 binding in ventral striatum.

Impulsivity: Increased rates of cocaine self-administration

- High-impulsivity rats self-administer more cocaine.

- impulsivity may be a pre-existingcondition for addiction

Stress is an environmental factor

Stress influences all aspects of the addiction process

Stress: Enhanced vulnerability

history of social defeat stress showed greater conditioned place preference (CPP) for low-dose cocaine.

Environmental enrichment: Protective

Reduced conditioned place preference (CPP) for cocaine.

Memory and cognitive processes: Involvement of PFC and striatum. Prefrontal cortex (PFC)

- Behavioral inhibition

- Self-control; executive function

Memory and cognitive processes: Involvement of PFC and striatum. Nucleus accumbens (ventral striatum)

Reward, motivation, cues

Memory and cognitive processes: Involvement of PFC and striatum. Dorsomedial striatum (DMS)

Goal-directed learning

Memory and cognitive processes:Involvement of PFC and striatum. Dorsolateral striatum (DLS)

Habit learning

Habit behavior vs. goal-directed

- Habit (stimulus-response association)

- Goal-directed(response-outcome association)

Chronic stress increases habitual behavior

causes enhanced habit learning

Chronic stress affects prefrontal cortex

causes loss of PFC volume and reduced dendritic complexity.

Chronic stress affects striatum

changes neuronal density in dorsal striatum→ DLS becomes more dominant than DMS.

3. Drug-induced neuroadaptations (1)

drug-induced factors that increase addiction likelihood:

Sensitization of drug effects

Enhanced habit learning

Reduced behavioral inhibition (Resistance to negative consequences)

Enhanced drug motivation

- intermittent cocaine use (3 days)

- followed by abstinence (7 days)

Results in:

- Increased cocaine potency

- Increased drug motivation

Habit learning

history of cocaine exposure biased toward habitual responding

Behavioral inhibition: Resistance to negative consequences

Some rats continue to self-administer cocaine despite getting footshock

(a negative consequence).

They are resistant to punishment.

Behavioral inhibition: Role for PFC. Optogenetic

Stimulation of PFC makes resistant animals more sensitive to footshock

Behavioral inhibition: Role for PFC. Optogenetic inhibition of PFC

makes sensitive animals resistant to footshock