Neurobiology of Addiction

Question 0

Acute withdrawl from drugs of abuse

Answer 0

Increases the reward response; increases anxiety in amygdala

Question 1

Acute rewarding effects of drug abuse

Answer 1

Mediated by dopamine from the nucleus accumbens septi

Question 2

Compulsive drug use assoc. w/ dependence

Answer 2

Loss of reward systems; recruitment of stress pathway in amydala via dynorphins and NE

Question 3

Major circuits involved w/ addiction

Answer 3

1. Mesolimbic dopamine
2. Ventral striatum
3. Ventral striatum- inferior frontal cortex- thalamus circuit
4. Dorsolateral frontal cortex- inferior frontal cortex- hippocampus
5. Extended amygdala

Question 4

Negative effects/withdrawl from drug abuse

Answer 4

Extended amygdala sends efferents to GPi and lateral hypothalamus

• Important control in the pathway regulating the “fear of pain”
• Also assoc. w/ decreased dopamine (mesolimbic) and 5/HT (nucleus accumbens)

Question 5

KOPr Addiction Cycle

Answer 5

1. Initial- Dynorphin levels rise as counter-regulatory mechanism to dopaminergic urges
2. Withdrawl- High dynorphin levels persist; vulnerability to relapse
3. Relapse- Exacerbated by high dynorphin levels; increased addiction

Overall has an anti-hedonic effect

Question 6

Largest hurdle in breaking addiction

Answer 6

Anticipation/Craving

• Enhanced sensitivity assoc. w/ environmental clues
• Changes in neurocircuitry and neuroplasticity due to glutaminergic projections from BLA and PFC

Question 7

Drug-induced reinstatement

Answer 7

Mediated by the nucleus accumbens-prefrontal cortex-ventral pallidum

…via glutamate