Food and drug cravings: Metaphor or common mechanisms?

Marcia Levin Pelchat, Ph.D.Monell Chemical Senses

CenterMay 3, 2004

A food craving is an intense desire to eat a particular

food.

Significance

Extremely common (Pelchat, 1997)

~ 100% of young women~70% of young men

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).

Is boredom enough?

Is hunger or a nutritional deficit necessary for craving?

Hunger and nutritional deprivation are not necessary

From Pelchat & Schaeffer, 2000

Is it more than a coincidence that

strong desires of all kinds are referred to

as cravings?Evidence for common mechanisms:

Drugs and Sweets

Large literature in rodents – alcohol and cocaine (Bachmanov et al., 1996; Gosnell, 2000).

Addiction treatment programs recommend use of sweets and deprived addicts report cravings for sweets (Weiss, 1982).

Motivational trade-offs (e.g. Kanarek 1996).

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• Withdrawal - Rats who had been eating a 25% sucrose diet shiver and shake when the diet is suddenly withdrawn or when given naloxone (Colantouni, Rada, et al., 2002).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.

Serotonin Brain serotonin may also

influence use or intake of alcohol, morphine, amphetamine, and cocaine (e.g. Volpicelli, 2001; Weiss & Koob, 2001).

Carbohydrate craving as self-medication: increase in brain serotonin (Wurtman, 1990).

Serotonergic agents have effects on food intake.

Dopamine Mesolimbic dopamine important in reward systems

for a variety of drugs of abuse including opioids, alcohol, amphetamine, and cocaine.

Patients on anti-psychotics gain weight.

Obese individuals have reduced D2 receptor availability (Wang, et al., 2002).

Decrease in raclopride binding potential in dorsal striatum after eating -correlated with meal pleasantness (Small et al. 2003).

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).

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).

Craving may be an acquired response based on repeatedly eating the craved food when hungry (Gibson & Desmond, 1999; Pelchat & Schaeffer, 2000).

Drug craving A number of imaging

techniques have been used to study drug and alcohol craving. Cue-induction.

Given the evidence for common substrates, such measures should be useful for visualizing desire for foods as well.

(From Childress et al, 1999)

fMRI study of food cravingM.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?

Behavioral results

All participants in the MD group experienced cravings when imagining the liked foods.

No one experienced cravings when imagining the monotonous diet.

We were very successful at turning craving on and off in 30 sec bins.

fMRI data analysis

Multi-subject, two-stage, random effects approach.

SPM99 software

Results expressed SPM {Z} scores, thresholded at p<0.001

MD group showed greater activation to the craved or liked foods.

Unpublished data omitted

Brain activation associated with food craving

Unpublished data omitted

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

Caudate nucleus

Dopamine in dorsal striatum clearly involved in feeding (Wang, et al., 2002; Volkow et al., 2003; Small et al., 2003).

Dorsal striatum – involved in habit learning (White, 1996).

Conclusions - fMRI

Subjects explicitly asked about food craving.

Independent of hunger. Evidence for common

substrates (Breiter et al., 1997; Garavan et al., 2000).

Importance of memory and habit in food craving.