HOW DOES ADDICTION OCCUR?

Dopamine Pathways

Functions•reward (motivation)•pleasure, euphoria•motor function (fine tuning)•compulsion•perseveration•decision making

nucleusaccumbens

hippocampus

striatum

frontalcortex

substantianigra/VTA

raphe

Neuronal structure

(receiving)

(sending)

/serotonin

Vmat

transporterstimulation

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

• Release DA from vesicles and reverse transporter

Drug Types:• Amphetamines -methamphetamine -MDMA (Ecstasy)

Vmat

transporter

serotonin/

• 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

BC

PrefrontalCortex Cbehavior

expressed Bbehaviorexpressed

Activation of Dopamine reward pathway initiates a behavior track

dopamine initiated

(Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167)

Orbito-frontal cortex

• Principles of Behavior Dynamics

AC

B

PrefrontalCortex

How does a behavior become an addiction?

BBB BAddictionbehaviorexpressed

dopamine

Orbito-frontal cortex

Prolonged Drug Use Changesthe Brain and

In Fundamentaland Long-Lasting Ways

We Have Generated A Lot of Evidence Showing That…

We Have Evidence That These Changes Can Be Both

Structural and Functional

AND…

Positron Emission Tomography

BRAIN IMAGING

Magnetic Resonance Imaging

control cocaine abuser

Decreases in Metabolism in Orbito Frontal Cortex (OFC)

Volkow et al. Am. J. Psychiatry 148, 621

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)

Implication:

Brain changes resulting from prolonged use of psychostimulants,

such as methamphetamine may be reflected in compromised cognitive and motor functioning.

Reward System in Addiction

Cocaine

Food

Ac t

i vit

y o

f R

e war

d S

yst e

m

METH

Alcohol

Ability to Experience Rewards Is Damaged

con

trol

s

trea

ted

More

Less

Get Rewired by Drug Use

Their Brains…

INHERITED FACTORS(genetic vulnerability-not inevitability)

• Common strategy to investigate are Twin Studies

1722

r-SA

r-candidate

5 6 3 samples, > 2 labs4 samples, > 3 labs>2 samples, >2 labs

Chromosomal Locations for Substance Abuse Vulnerability Loci

Uhl et al Tr Genetics, updated June 03

VULNERABILITY to What?Starting Drug Use?

Liking Drugs More?

Continuing Drug Use?

Becoming Addicted?

Specific to A Particular Drug?