Opioids and Sucrose: Opioids and Sucrose: Why do candy bars Why do candy bars taste better than taste better than

carrots?carrots?

John CadwalladerJohn Cadwallader

General StructureGeneral Structure

► 1) Illustration of basic phenomenon:1) Illustration of basic phenomenon: Intact opioid systemIntact opioid system Disabled opioid systemDisabled opioid system

► 2) Brief History of Endogenous Opioid System2) Brief History of Endogenous Opioid System► 3) Theoretical explanation of phenomenon3) Theoretical explanation of phenomenon

Opioid self-administrationOpioid self-administration Food intake regulationFood intake regulation Berridge and Robinson’s TheoryBerridge and Robinson’s Theory

► 4) Interesting studies4) Interesting studies HumanHuman Brain PlasticityBrain Plasticity Social IsolationSocial Isolation

The Endogenous Opioid System: The Endogenous Opioid System: Brief HistoryBrief History

►Opium derived from the poppy seed Opium derived from the poppy seed Papaver Papaver somniferumsomniferum. First reference to the substance . First reference to the substance dates back to 300B.C.dates back to 300B.C.

► An important active principle in opium was An important active principle in opium was isolated in 19isolated in 19thth century and named morphine century and named morphine (after Morpheus, Greek god of dreams). (after Morpheus, Greek god of dreams).

► Attempts to separate analgesic properties of Attempts to separate analgesic properties of these compounds from their addictive these compounds from their addictive properties lead to creation of heroin, properties lead to creation of heroin, meperidine, and methadone. meperidine, and methadone.

The Endogenous Opioid System: The Endogenous Opioid System: Brief HistoryBrief History

►Opioid receptors in the mammalian Opioid receptors in the mammalian brain discovered in 1970.brain discovered in 1970.

►The existence of these receptors and The existence of these receptors and the fact that opioid antagonists exert the fact that opioid antagonists exert effects on opiate-naieve subjects lead effects on opiate-naieve subjects lead to discovery of endogenous (naturally to discovery of endogenous (naturally occurring in the brain) opioids.occurring in the brain) opioids.

►Beta-endorphin, enkephalins, Beta-endorphin, enkephalins, dynorphins, moredynorphins, more

The Endogenous Opioid System: The Endogenous Opioid System: Brief History Brief History

►Multiple receptor subtypes:Multiple receptor subtypes:►General antagonists:General antagonists:

NaloxoneNaloxone NaltrexoneNaltrexone

The Yamamoto ExperimentThe Yamamoto Experiment

► Taken 90m after Taken 90m after start of drinking of start of drinking of compoundcompound

►No difference No difference between saccharin between saccharin and sucroseand sucrose

►Gastric infused rats Gastric infused rats show results caused show results caused by taste-information by taste-information and not post-and not post-ingestive effectsingestive effects

The Yamamoto ExperimentThe Yamamoto Experiment

► After a CTA, beta After a CTA, beta endorphin is no endorphin is no longer releasedlonger released

The Yamamoto ExperimentThe Yamamoto Experiment

►ConclusionsConclusions Beta-endorphin released in brain upon Beta-endorphin released in brain upon

ingestion of certain solutionsingestion of certain solutions More beta-endorphin released for tastes More beta-endorphin released for tastes

rats are known to prefer (saccharin and rats are known to prefer (saccharin and sucrose)sucrose)

Disabled Opioid SystemDisabled Opioid System

► Lynch 1985Lynch 1985 Difference in intake Difference in intake

between rats on a between rats on a normal day and rats normal day and rats treated with treated with naloxonenaloxone

Variable Variable concentrations of concentrations of saccharinesaccharine

Naloxone dose-Naloxone dose-dependent responsedependent response

Disabled Opioid SystemDisabled Opioid System

► Yirmiya et al 1987Yirmiya et al 1987 Opioid receptors Opioid receptors

genetically knocked genetically knocked out (CXBK) compared out (CXBK) compared to normal (C57)to normal (C57)

Injected with saline or Injected with saline or naltrexonenaltrexone

Saccharin preference Saccharin preference completely knocked completely knocked out in CXBK – Nal out in CXBK – Nal micemice

Disabled Opioid SystemDisabled Opioid System

►ConclusionsConclusions Opioid activity is necessary for Opioid activity is necessary for

saccharin/sucrose preferencesaccharin/sucrose preference

►Why is opioid activity necessary?Why is opioid activity necessary?

Opioids and ReinforcementOpioids and Reinforcement

►Drug Self-AdministrationDrug Self-Administration►Food regulationFood regulation►Berridge’s TheoryBerridge’s Theory

Drug Self-AdministrationDrug Self-Administration

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

General Food Intake General Food Intake RegulationRegulation

Berthoud 2002

Berridge and Robinson’s Berridge and Robinson’s TheoryTheory

► Reward involves Reward involves three componentsthree components 1) Hedonic activation1) Hedonic activation 2) Associative 2) Associative

learning between learning between conditioned stimuli conditioned stimuli and unconditioned and unconditioned stimuli (how sugar stimuli (how sugar looks with how it looks with how it tastes)tastes)

3) “Attribution of 3) “Attribution of incentive salience”incentive salience”

Berridge and Robinson’s Berridge and Robinson’s TheoryTheory

► Forebrain Forebrain modulation still modulation still present in 6-OHDA present in 6-OHDA ratsrats

Summary:Summary:

►Opioid systems control hedonic effect Opioid systems control hedonic effect of sucrose. This is associated with of sucrose. This is associated with general conditioned stimuli so next general conditioned stimuli so next time the stimuli are encountered, time the stimuli are encountered, dopamine systems mediate ‘wanting’ dopamine systems mediate ‘wanting’ of the stimuli.of the stimuli.

►Sugar tastes better than tomatoes Sugar tastes better than tomatoes because ingesting higher energy foods because ingesting higher energy foods used to be adaptiveused to be adaptive

Sucrose and Brain PlasticitySucrose and Brain Plasticity

► Rats fed Rats fed high high sucrose sucrose diet diet possibly possibly have have greater greater opioid opioid receptor receptor density.density.

► Kanarek Kanarek et al 2001et al 2001

Sucrose, Opioids, and Social Sucrose, Opioids, and Social IsolationIsolation

► Sucrose Sucrose decreases decreases distress distress vocalizationsvocalizations

Human StudiesHuman Studies