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

fact

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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

tio

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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

Fixa

tio

nTi

me

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Becker et al, 2014Neuropsychopharmacol

Reward responsiveness:«Objective anhedonia test»

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Morphine Placebo Naltrexone

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mu

lus

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g re

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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.