Opioids and Sucrose: Why do candy bars taste better than carrots? John Cadwallader

General Structure ► 1) Illustration of basic phenomenon:  Intact opioid system  Disabled opioid system ► 2) Brief History of Endogenous Opioid System ► 3) Theoretical explanation of phenomenon  Opioid self-administration  Food intake regulation  Berridge and Robinson’s Theory ► 4) Interesting studies  Human  Brain Plasticity  Social Isolation

The Endogenous Opioid System: Brief History ► Opium derived from the poppy seed Papaver somniferum. First reference to the substance dates back to 300B.C. ► An important active principle in opium was isolated in 19 th century and named morphine (after Morpheus, Greek god of dreams). ► Attempts to separate analgesic properties of these compounds from their addictive properties lead to creation of heroin, meperidine, and methadone.

The Endogenous Opioid System: Brief History ► Opioid receptors in the mammalian brain discovered in ► The existence of these receptors and the fact that opioid antagonists exert effects on opiate-naieve subjects lead to discovery of endogenous (naturally occurring in the brain) opioids. ► Beta-endorphin, enkephalins, dynorphins, more

The Endogenous Opioid System: Brief History ► Multiple receptor subtypes: ► General antagonists:  Naloxone  Naltrexone

The Yamamoto Experiment ► Taken 90m after start of drinking of compound ► No difference between saccharin and sucrose ► Gastric infused rats show results caused by taste-information and not post-ingestive effects

The Yamamoto Experiment ► After a CTA, beta endorphin is no longer released

The Yamamoto Experiment ► Conclusions  Beta-endorphin released in brain upon ingestion of certain solutions  More beta-endorphin released for tastes rats are known to prefer (saccharin and sucrose)

Disabled Opioid System ► Lynch 1985  Difference in intake between rats on a normal day and rats treated with naloxone  Variable concentrations of saccharine  Naloxone dose- dependent response

Disabled Opioid System ► Yirmiya et al 1987  Opioid receptors genetically knocked out (CXBK) compared to normal (C57)  Injected with saline or naltrexone  Saccharin preference completely knocked out in CXBK – Nal mice

Disabled Opioid System ► Conclusions  Opioid activity is necessary for saccharin/sucrose preference ► Why is opioid activity necessary?

Opioids and Reinforcement ► Drug Self-Administration ► Food regulation ► Berridge’s Theory

Drug Self-Administration ► Antagonizing opioid receptors in the ventral tegmental area (VTA) and nucleus accumbens (NAc) will cause animals to increase response rate for drug (extinction burst)

General Food Intake Regulation Berthoud 2002

Berridge and Robinson’s Theory ► Reward involves three components  1) Hedonic activation  2) Associative learning between conditioned stimuli and unconditioned stimuli (how sugar looks with how it tastes)  3) “Attribution of incentive salience”

Berridge and Robinson’s Theory ► Forebrain modulation still present in 6-OHDA rats

Summary: ► Opioid systems control hedonic effect of sucrose. This is associated with general conditioned stimuli so next time the stimuli are encountered, dopamine systems mediate ‘wanting’ of the stimuli. ► Sugar tastes better than tomatoes because ingesting higher energy foods used to be adaptive

Sucrose and Brain Plasticity ► Rats fed high sucrose diet possibly have greater opioid receptor density. ► Kanarek et al 2001

Sucrose, Opioids, and Social Isolation ► Sucrose decreases distress vocalizations

Human Studies