Hva styrer det endogene opioidsystemet i den friske ... · bruk av ikke-opioide rusmidler (alkohol,...
Transcript of Hva styrer det endogene opioidsystemet i den friske ... · bruk av ikke-opioide rusmidler (alkohol,...
Hva styrer det endogene opioidsystemet i den friske
menneskehjernen?
Siri Leknes
What the tabloids know
Social and Affective Neuroscience
fMRI
OxytocinOpioids
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2007 2009 2011 2013 2015 2017
Imp
act
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Opioids & the neurobiology of addiction
Dopamine pathways
MOR disinhibition of dopamine
MOR distribution (μ-opioidreceptors)
Opioid regulation of pain
Zubieta et al 2005, J Neurosci
Leknes and Tracey, 2008, Nat Rev Neuroscience
Wanigasekera et al, 2013, PNAS
Opioids for pain, reward and social attachment
Leknes and Tracey, 2008, Nat Rev Neurosci;
OpioidsDopamine
≠ ?
Løseth, Ellingsen, Leknes, 2014, Frontiers Behavioural Neuroscience
BOTSA
Cooper and Turkish, 1989, Pharmacol Biochem BehaviorMahler and Berridge, 2012, Psychopharmacology
Opioid regulation of social emotions
Hsu et al, 2013, Molecular Psychiatry
Animal research Human research
• Opioid drugs modulate high-value reward motivation– Food
– Partner
• ‘Runner’s high’ euphoria
• Blocking opioids reduces food liking – Especially high-value foods
Opioid regulation of reward
Videos from www.berridgelab.org
Psychopharmacology
1. How does a pharmacologicaltreatment work?
2. How does the endogenoussystem work?– Drug treatment– Natural variability
• Blood/CSF measures
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Citalopram Placebo
Fixa
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Jonassen et al, 2015, Psychopharmacology
• N=25 females• Between-subjects
What is the μ-opioid system for?
50 mg naltrexone
10 mg morphine
Opioid effects on reward behaviours
• N=30 males within-subjects
Chelnokova et al. 2014, Molecular Psychiatry
How do we typically look at faces?
• Why attend to the eyes?
μ-opioid system promotes social attention
Chelnokova et al. , submitted• N=30 males within-subjects
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Eyes&Brows NoseMouthJaw ForeheadCheeks
Morphine
Placebo
Naltrexone
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Becker et al, 2014Neuropsychopharmacol
Reward responsiveness:«Objective anhedonia test»
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Morphine Placebo Naltrexone
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OMT patientsComparison group
N = 30 males within-subject
N = 25 mothers in OMT
N = 29 comparison
mothers
Eikemo, Biele et al, in revision Eikemo, Pedersen et al, in preparation
Can opioids make pain relief rewarding?
Zubieta et al 2005, J Neurosci
Leknes et al 2008, Eur J Neurosci
Solomon & Corbit 1974, Psychol Rev
When context renders pain a safety signal
Leknes et al, 2013, PainWinston et al, 2014, J NeuroscienceBerna*, Leknes* et al, in preparation
Context
Z=-16 Z=-14
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naloxone placebo
Opioid-dependent context effect?
Control
Relief context
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Addiction/habituation to endogenous opioids?
• Mice exposed to UV light for 6 weeks• Β-endorphin levels rose after a week• Naloxone treatment then produced aversion (CPA)
Fell et al, 2014, Cell
What does the human μ-opioid system do?
• Regulates pain and distress
– Reward- and stress-induced pain relief (Fields)
Yelle et al, 2008, J Neurosci; Derbyshire et al, 2009, Neuroimage; Martucci et al, 2012, Pain
Grill et al, 2002, J Neurophysiol;
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Offset analgesia
What does the human μ-opioid system do?
• Promotes motivation for most valuable– Monetary reward– Faces– Face region– Sweet tastes
• Clinical significance– Decision making and social
function• Drug abuse• Chronic pain• Autism
The Hedonic Pharmacology team
Kongsberg sykehus
Thank you!
Irene TraceyMichael LeeChantal Berna
Dan-Mikael Ellingsen Håkan OlaussonJohan Wessberg
Bruno LaengLotte ThomsenGuido BieleTor Endestad
Frode WillochTrine Hjørnevik
Vigdis VindenesElisabeth ØiestadLiliana Bachs
Marie EikemoOlga ChelnokovaGuro LøsethJeppe RiegelsHedda MaurudSelma Øverland Lie
Philipp LobmaierNicolaj KunøeMonica Sarfi
Thank you
Johannes Gjerstad
Steven R WilsonElin Johnsen
Spørsmål
• 1) Hvilken rolle spiller opioidsystemet ved bruk av ikke-opioide rusmidler (alkohol, amfetamin, nikotin)?
• 2) Beskriv opioidsystemets viktigste (kjente) funksjoner på tvers av artene, dvs. hos rotter, aper og mennesker.
• 3) Diskuter årsaker til at forskjellige opioidagonister fremkaller forskjellige subjektive effekter hos mennesker.