# Presentation: 924062

## Dopamine’s Role in

**NATIONAL INSTITUTE**
**ON DRUG ABUSE**

**NIDA**

**NIAAA**

**National Institute Alcohol**
**Abuse and Alcoholism**

**Nora D. Volkow, M.D.**
**Director, National Institute on Drug Abuse**

**Dopamine’s Role in**

**DRUG  CRAVING**

## Dopamine

** ****Neurotransmission**

## DA and Drug Reinforcement

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**“****High”**

**DA and Drug Reinforcement**

**raclopride**

**raclopride**

**DA**

**DA**

**DA initiates and maintains responses to salient stimuli such as drugs**

## 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

** **
**Since DA is involved with reward and ****with prediction of reward****,  it could underlie craving**

## Background

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

***Philipps et al Nature 422, 614-618***

**In training the cue was paired with cocaine**

**In training the cue ****was not**** paired with cocaine**

## 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 

***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 **
**	**

**1. Subjects**

## Methods: Videos

**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**

## Self-reports of craving during the neutral and the cocaine-cue video

**Self-reports of craving during the neutral and the cocaine-cue video**

**Cocaine Craving**

***P < 0.01***

**Before**

**After**

***Cocaine cues increased self reports of ******cocaine craving in cocaine abusers***

**Cocaine Craving**

**(1-7)**

**Before**

**After**

***Neutral Video***

***Cocaine-Cue Video***

***Source: Volkow, ND et al., Journal of Neuroscience, 26(24):6583-6588, 2006.***

## Cue-induced increases in DA were associated with craving

***P < 0.002***

**Relationship between Cue-Induced Decreases in [11C]raclopride Binding and Cocaine Craving**

***P < 0.05***

***Source: Volkow, ND et al., Journal of Neuroscience, 26(24):6583-6588, 2006.***

## 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?**

##    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 			

***   ******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**

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

## [11C]Raclopride Binding in Food Deprived Controls During Neutral and Food Cues

**Neutral**

**Food Cue**

**[****11****C]Raclopride Binding in Food Deprived Controls During Neutral and Food Cues**

***Source: Volkow, et al., Synapse 2002.***

## Relationship Between DA Changes and Self-Reports of Hunger and Desire for Food Induced by Food Cues

**Hunger**

**Desire for Food**

**% Change Bmax/kd**

- p < 0.01

##    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 it’s a drug or food 

***   ******in the behaviors necessary to procure the ***
***   ******desired object whether it’s a drug or food ***

***Cue-induced DA increases were associated with craving for drugs as well as for food, which highlights the automated (reflexes) nature of these responses ***

***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 ***

## Funded by DOE and NIH

**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**

## Brain Dopamine Response to Food Stimulation

**(Bmax/Kd)**

**Placebo/Neutral**

**MP/Food**

**p < 0.005**

- 1.5

- 0

- ml/g

***Source: Volkow, et al., Synapse 2002.***

**Desire for Food**

**% Change Bmax/kd**

**p < 0.01**

**Neutral**

**Food**

## 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

**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**

**2. Subjects**