1. HOW DOES ADDICTION
OCCUR?

2. Dopamine Pathways
Functions
•reward
(motivation)
•pleasure,
euphoria
•motor function
(fine tuning)
•compulsion
nucleus
accumbens
hippocampus
striatum
frontal
cortex
substantia
nigra/VTA
raphe

3. Neuronal structure
(receiving)
(sending)

4. /serotonin
Vmat
transporter
stimulation
How some drugs of abuse cause dopamine release:
• opioids narcotics (activate opioid receptors)
• nicotine (activate nicotine receptors)
• marijuana (activate cannabinoid receptors)
• caffeine
• alcohol (activate GABA receptors; an inhibitory transmitter)
Drug :
• cocaine
• ritalin
vesicle Neuronal terminal

5. • Release DA from vesicles and reverse
transporter
Drug Types:
• Amphetamines
-methamphetamine
-MDMA (Ecstasy)
Vmat
transporter
serotonin/

6. • Principles of Behavior Dynamics
Behavior Tracts Compete for Expression
 Expression is Determined by (i) Dominance of Tracts,
(ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or
saliency (orbitofrontal cortex)
A
B
C
Prefrontal
Cortex
Cbehavior
expressed Bbehavior
expressed
Activation of Dopamine reward pathway initiates a behavior
track
dopamine initiated
(Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 1
Orbito-
frontal cortex

7. • Principles of Behavior Dynamics
A
C
B
Prefrontal
Cortex
How does a behavior become
an addiction?
BB B BAddiction
behavior
expressed
dopamine
Orbito-
frontal cortex

8. Prolonged Drug Use Changes
the Brain and
In Fundamental
and Long-Lasting Ways
We Have Generated A Lot of
Evidence Showing That…

9. We Have Evidence That
These Changes Can Be Both
Structural and Functional
AND…

10. Positron Emission Tomography
BRAIN IMAGING
Magnetic Resonance Imaging

11. control cocaine abuser
Decreases in Metabolism
in Orbito Frontal Cortex (OFC)
Volkow et al. Am. J. Psychiatry 148, 621

12. Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998.
METH Suppresses Expression of DAT
(note: duration of use/3-20 yrs; abstinent/ 1-4 yrs)

13. Implication:
Brain changes resulting from
prolonged use of psychostimulants,
such as methamphetamine
may be reflected in compromised
cognitive and motor functioning.

14. Reward System in Addiction
Cocaine
Food
METH
Alcohol
Ability to Experience
Rewards Is Damaged
treated
More
Less

15. Get Rewired
by Drug Use
Their Brains…

16. INHERITED FACTORS
(genetic vulnerability-not
inevitability)
• Common strategy to investigate
are Twin Studies

17. 17
22
r-SA
r-candidate
5 6 3 samples, > 2 labs
4 samples, > 3 labs
>2 samples, >2 labs
Chromosomal Locations for Substance Abuse
Vulnerability Loci
Uhl et al Tr Genetics, updated June 03

18. VULNERABILITY to What?
Starting Drug Use?
Liking Drugs More?
Continuing Drug Use?
Becoming Addicted?
Specific to A Particular Drug?