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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?