Transcript Opioids and Sucrose: An Overview

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
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 19th 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.
► Opium
The Endogenous Opioid System:
Brief History
► Opioid
receptors in the mammalian brain
discovered in 1970.
► 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 dosedependent 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