1. Food and drug cravings: Metaphor or common mechanisms? Marcia Levin Pelchat, Ph.D. Monell Chemical Senses Center May 3, 2004

2. A food craving is an intense desire to eat a particular food.

3. Significance l Extremely common (Pelchat, 1997)  ~ 100% of young women  ~70% of young men l Influence snacking behavior, compliance with dietary restrictions, binge eating, and lifetime prevalence of bulimia nervosa (Basdevant, Craplet, & Guy-Grand, 1993; Waters, Hill, & Waller, 2001; Wurtman, 1988; Gendall & Joyce, 2001).

4. Is boredom enough? Is hunger or a nutritional deficit necessary for craving?

5. Hunger and nutritional deprivation are not necessary From Pelchat & Schaeffer, 2000

6. Is it more than a coincidence that strong desires of all kinds are referred to as cravings? Evidence for common mechanisms:

7. Drugs and Sweets l Large literature in rodents – alcohol and cocaine (Bachmanov et al., 1996; Gosnell, 2000). l Addiction treatment programs recommend use of sweets and deprived addicts report cravings for sweets (Weiss, 1982). Motivational trade-offs (e.g. Kanarek 1996).

8. Endogenous opiates. Drugs of abuse strongly stimulate this system either directly or indirectly. Diet-induced analgesia – Sugar water is thought to produce release of endogenous opiates in human infants. Some evidence in adults as well. Blockers influence food intake and pleasantness (Drewnowski et al.,1995 ) (Yeomans & Gray, 1997). Withdrawal - R ats who had been eating a 25% sucrose diet shiver and shake when the diet is suddenly withdrawn or when given naloxone (Colantouni, Rada, et al., 2002). Benzodiazepines increase intake by inhibiting GABA which leads to higher levels of opiates. Little explicit work on cravings.

9. Serotonin l Brain serotonin may also influence use or intake of alcohol, morphine, amphetamine, and cocaine (e.g. Volpicelli, 2001; Weiss & Koob, 2001). l Carbohydrate craving as self- medication: increase in brain serotonin (Wurtman, 1990). l Serotonergic agents have effects on food intake.

10. Dopamine l Mesolimbic dopamine important in reward systems for a variety of drugs of abuse including opioids, alcohol, amphetamine, and cocaine. l Patients on anti-psychotics gain weight. l Obese individuals have reduced D2 receptor availability (Wang, et al., 2002). l Decrease in raclopride binding potential in dorsal striatum after eating -correlated with meal pleasantness (Small et al. 2003). l Low baseline D2 receptors in dorsal striatum correlated with DEBQ emotionality score (Volkow et al., 2003). DEBQ emotionality score correlated with frequency of food cravings (Pelchat & Schaeffer, 2000).

11. Conditioning Conditioning effects have been used to explain continued compulsion to use drugs long after withdrawal (e.g. O’Brien et al., 1998). Nutritional deprivation is not necessary to produce food cravings (Pelchat & Schaeffer, 2000). Sight, smell or imagery may trigger food craving (Federoff et al., 1997; Tuomisto et al., 1999). l Craving may be an acquired response based on repeatedly eating the craved food when hungry (Gibson & Desmond, 1999; Pelchat & Schaeffer, 2000).

12. Drug craving l A number of imaging techniques have been used to study drug and alcohol craving. Cue- induction. l Given the evidence for common substrates, such measures should be useful for visualizing desire for foods as well. (From Childress et al, 1999)

13. fMRI study of food craving M.L. Pelchat, Monell Chemical Senses Center & J. D. Ragland, University of Pennsylvania 2 groups – monotonous diet (MD) for 1 1/2 days or unrestricted diet with sampling of monotonous diet (ND). BOLD fMRI - 4T Imagine two liked foods or imagine monotonous diet in block design. Why use imagination rather than video?

14. Behavioral results l All participants in the MD group experienced cravings when imagining the liked foods. l No one experienced cravings when imagining the monotonous diet. l We were very successful at turning craving on and off in 30 sec bins.

15. fMRI data analysis l Multi-subject, two-stage, random effects approach. l SPM99 software l Results expressed SPM {Z} scores, thresholded at p<0.001

16. MD group showed greater activation to the craved or liked foods. Unpublished data omitted

17. Brain activation associated with food craving Unpublished data omitted

18. Hippocampus Animal model of drug relapse: memory circuits more important than reward. Vorel et al., (2001): ventral subiculum stimulation (incentive) more effective than medial forebrain bundle stimulation (reward). Sensory trigger for desire

19. Caudate nucleus l Dopamine in dorsal striatum clearly involved in feeding (Wang, et al., 2002; Volkow et al., 2003; Small et al., 2003). l Dorsal striatum – involved in habit learning (White, 1996).

20. Conclusions - fMRI l Subjects explicitly asked about food craving. l Independent of hunger. l Evidence for common substrates (Breiter et al., 1997; Garavan et al., 2000). l Importance of memory and habit in food craving.