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
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
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
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
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