Dopamine

1
Dopamines Role in
DRUG CRAVING
Nora D. Volkow M.D. Director National Institute
on Drug Abuse
NIAAA
NIDA
National Institute Alcohol Abuse and Alcoholism
NATIONAL INSTITUTE ON DRUG ABUSE
2
Dopamine Neurotransmission
3
DA and Drug Reinforcement
High
T
Y
R
O
S
I
N
E
T
Y
R
O
S
I
N
E
D
O
P
A
D
O
P
A
D
A
D
A
DA
D
A
DA
D
A
D
A
D
A
D
A
D
A
D
A
raclopride
D
A
D
A
D
A
raclopride
D
A
R
D
A
D
A
D
A
R
R
R
R
R
DA initiates and maintains responses to salient
stimuli such as drugs
4

• The mechanism(s) underlying the intense desire
  for the drug when addicted subjects are exposed
  to drug cues (places people and paraphernalia
  linked with the drug) is still unknown.
• Since DA is involved with reward and with
  prediction of reward it could underlie craving

5
Background

• In rodents when a neutral stimuli is
  repeatedly paired with the drug (conditioned) it
  elicits DA increases.

In training the cue was paired with cocaine
In training the cue was not paired with cocaine
Philipps et al Nature 422 614-618
6
1. Subjects

• Eighteen cocaine abusers
• Inclusion criteria
• DSM- IV criteria for cocaine dependence
• active use for at least the prior 6 months
• free-base or crack
• at least four grams a week
• Exclusion criteria
• past or present neuro and psychiatric diseases
  other than cocaine dependence
• past or present endocrinological disease
• head trauma with loss of consciousness
• current medical illness

7
2. Subjects

• Gender 17 males 1 female
• Age 43 6 years
• Ethnicity 15 AA 3 Caucasians
• Education 13 2 years of education
• Years used 15 7 years
• Route 18 smoked cocaine
• Dose used 2.8 1.6 grams a day
• Last used 2 1.4 days (range 1 6 days)
• Cigarette smokers 15 current smokers

8
Methods Videos

• The neutral video featured non-repeating
  segments of nature scenes
• The cocaine-cue video featured non repeating
  scenes that simulated purchase preparation
• and smoking of cocaine

Videos were shown 10 min prior to radiotracer
injection for a total of 40 min
9
Self-reports of craving during the neutral and
the cocaine-cue video
Neutral Video
Cocaine-Cue Video
P lt 0.01
Cocaine Craving
Cocaine Craving
(1-7)
After
After
Before
Before
Cocaine cues increased self reports of cocaine
craving in cocaine abusers
Source Volkow ND et al. Journal of
Neuroscience 26(24)6583-6588 2006.
10
Cue-induced increases in DA were associated with
craving
Relationship between Cue-Induced Decreases in
11Craclopride Binding and Cocaine Craving
P lt 0.002
P lt 0.05
Source Volkow ND et al. Journal of
Neuroscience 26(24)6583-6588 2006.
11
Craving of Food

• Why is it that the sight of food can elicit the
  desire for it even when we are not hungry
• Are the responses to cues similar to those that
  triggered the cocaine in cocaine abusers

12
Ten healthy food deprived controls (15-18 hours
food deprivation) tested under neutral and food
cue conditions

• Neutral Subjects were asked to describe their
  family genealogy.
• Food Cues The food-cue featured non repeating
  presentation of favorite foods that had been
  heated to enhance smell

Stimuli were presented 10 min prior to
radiotracer injection for a total of 40 min
13
Brain Dopamine Response to Food Stimulation
Neutral
Food
1.5
0
ml/g
(Bmax/Kd)
p lt 0.005
Desire for Food
Placebo/Neutral
MP/Food
Change Bmax/kd
p lt 0.01
Source Volkow et al. Synapse 2002.
14
11CRaclopride Binding in Food Deprived Controls
During Neutral and Food Cues
Neutral
Bmax/Kd decreased with exposure to food-cues
presumably from DA increases
Food Cue
Source Volkow et al. Synapse 2002.
15
Relationship Between DA Changes and Self-Reports
of Hunger and Desire for Food Induced by Food Cues
Desire for Food
Hunger
Change Bmax/kd
p lt 0.01
16
Both drug as well as food cues increased DA in
dorsal striatum (brain region involved with
initiation of action and with learning of
habits) suggesting that drugs usurp
physiological processes
Cue-induced DA increases were associated with
craving for drugs as well as for food which
highlights the automated (reflexes) nature of
these responses

• DA activation of DS may underlie the desire
  (wanting) that result in the readiness to engage
• in the behaviors necessary to procure the
• desired object whether its a drug or food

17
Funded by DOE and NIH
F. Telang R. MacGregor P. Carter D.
Schlyer C. Shea J. Gatley S. Dewey C.
Redvanly P. King L. Caligiuri G-J Wang M.
Franceschi Y-S Ding J. Logan N. Volkow J.
Fowler R. Ferrieri C. Wong (not shown) D.
Alexoff C. Felder N. Pappas D. Franceschi N.
Netusil V. Garza R. Carciello D. Warner M.
Gerasimov