Neurobiology of Addiction

Transcription

1 Neurobiology of Addiction Tiffany Love, Ph.D. Department of Psychiatry The University of Utah

2 What is Addiction? Addiction is a chronic, relapsing, and treatable brain disorder. Compulsive drug seeking and use in spite of serious consequences

3 Three Stage Model of Addiction Stage 1 Binge / Intoxication Stage 3 Preoccupation / Anticipation Stage 2 Withdrawal / Negative Mood Koob & Le Moal 2008

4 Three Stage Model of Addiction Stage 1 Binge / Intoxication 1. Binge / Intoxication o Associated with positive reinforcement & motivational learning o Associating cues with reward delivery e.g., Cat on Catnip NAc VTA

5 Nucleus Accumbens Ventral Tegmental Area * Dopamine Dopamine Receptor

6 Nucleus Accumbens Ventral Tegmental Area * Dopamine Dopamine Receptor What does dopamine signal? Value of future reward / of work to gain the reward Motivation to obtain reward WANT Evolved out of survival

7 Dopamine is released in response to many types of rewards Di Chiara and Imperato, PNAS 1988, Slides NIDA

8 Drugs of abuse can be more reinforcing than natural rewards DA DA Drugs of abuse can release up to 10 times the amount of DA that natural rewards do Overstimulation of the reward circuit: o Leads to an increase in the drive to obtain drugs over natural rewards

9 DA neurons will eventually fire in response to cues that predict the reward Conditioned stimuli paired formerly paired with the drug elicit DA release o Trigger craving o Increase motivation to seek out drug o May lead to binge use

10 Three Stage Model of Addiction Stage 1 Binge / Intoxication 2. Negative Affect & Withdrawal o Associated with negative reinforcement and increases in stress Stage 3 Preoccupation / Anticipation Stage 2 Withdrawal / Negative Mood Koob & Le Moal 2008

11 Neuroadaptations as a result of prolonged drug use: Dopamine At baseline, dopamine receptor concentration is reduced to compensate for the frequent, large dopamine surges elicited by drug use Volkow et al 2009 Control Drug Abuser

12 Normal Reward Circuits Dopamine Dopamine Receptor Prolonged Drug Use Reward Circuits Baseline Normal Feeling HIGH *Elevated Reward Threshold

13 Normal Reward Circuits Dopamine Dopamine Receptor Prolonged Drug Use Reward Circuits Baseline Normal Feeling HIGH *Elevated Reward Threshold

14 HPA/Stress Axis Hypothalamus Stress Systems Dysregulated CRF Anterior Pituitary ACTH Low CRF High CRF Adrenal Cortex CORT Baseline Normal Feeling *Negative Motivational / Affective state DYSPHORIA

15 HPA/Stress Axis Hypothalamus Stress Systems Dysregulated CRF Anterior Pituitary ACTH Low CRF High CRF Adrenal Cortex CORT Baseline Normal Feeling *Negative Motivational / Affective state DYSPHORIA

16 HPA/Stress Axis Hypothalamus Stress Systems Dysregulated CRF Anterior Pituitary ACTH Low CRF High CRF Adrenal Cortex CORT Baseline Normal Feeling *Negative Motivational / Affective state DYSPHORIA

17 Long-term Result of Neuroadaptations Baseline Normal Feeling HIGH DYSPHORIA Time Amount of drug needed to feel normal

18 Three Stage Model of Addiction Stage 1 Binge / Intoxication 3. Preoccupation & Anticipation o Associated with changes to executive functioning Stage 3 Preoccupation / Anticipation Stage 2 Withdrawal / Negative Mood Koob & Le Moal 2008

19 Normal Control Automatic STOP

20 Iowa Gambling Task

21 Iowa Gambling Task $ GOOD WINS: Small, Frequent LOSSES: Moderate, Rare

22 Iowa Gambling Task BAD WINS: Large, Rare LOSSES: Large, Frequent $

23 Iowa Gambling Task $ GOOD WINS: Small, Frequent LOSSES: Moderate, Rare BAD WINS: Large, Rare LOSSES: Large, Frequent $

24 Iowa Gambling Task BAD WINS: Large, Rare LOSSES: Large, Frequent $ Bechara 2008

25 What happens if there is PFC dysfunction? Bechara 2008

26 What happens if there is PFC dysfunction? Control Cocaine Abuser

27 What happens if there is PFC dysfunction? Control Cocaine Abuser

28 What happens if there is PFC dysfunction? Control Cocaine Abuser

29 Summary: Why is it so difficult to quit?

30 Non-Addicted Addicted Control Control WANT Drive WANT Drive Memory STOP Memory GO

31 Thank you