Hva styrer det endogene opioidsystemet i den friske menneskehjernen? Siri Leknes

Transkript

1 Hva styrer det endogene opioidsystemet i den friske menneskehjernen? Siri Leknes

2 What the tabloids know

3 Social and Affective Neuroscience Impact factor fmri Oxytocin Opioids

4 Opioids & the neurobiology of addiction Dopamine pathways MOR distribution (μ-opioid receptors) MOR disinhibition of dopamine

5 Opioid regulation of pain Leknes and Tracey, 2008, Nat Rev Neuroscience Zubieta et al 2005, J Neurosci Wanigasekera et al, 2013, PNAS

6 Opioids for pain, reward and social attachment BOTSA Opioids Dopamine? Leknes and Tracey, 2008, Nat Rev Neurosci; Cooper and Turkish, 1989, Pharmacol Biochem Behavior Mahler and Berridge, 2012, Psychopharmacology Løseth, Ellingsen, Leknes, 2014, Frontiers Behavioural Neuroscience

7 Opioid regulation of social emotions Hsu et al, 2013, Molecular Psychiatry

8 Opioid regulation of reward Animal research Opioid drugs modulate high-value reward motivation Food Partner Human research Runner s high euphoria Blocking opioids reduces food liking Especially high-value foods Videos from

9 Psychopharmacology N=25 females Between-subjects 1. How does a pharmacological treatment work? 2. How does the endogenous system work? Drug treatment Natural variability Blood/CSF measures Fixation Time (%) Citalopram Placebo Jonassen et al, 2015, Psychopharmacology

10 What is the μ-opioid system for? Opioid effects on reward behaviours N=30 males within-subjects 10 mg morphine 50 mg naltrexone

11 Chelnokova et al. 2014, Molecular Psychiatry

12 How do we typically look at faces? Why attend to the eyes?

13 μ-opioid system promotes social attention Fixation Time (%) *** Morphine Placebo Naltrexone Eyes&Brows NoseMouthJaw ForeheadCheeks Becker et al, 2014 Neuropsychopharmacol N=30 males within-subjects Chelnokova et al., submitted

14 Reward responsiveness: «Objective anhedonia test» 0,20 0,20 preference for high value stimulus [log reponse bias] 0,15 0,10 0,05 0,15 0,10 0,05 0,00 Morphine Placebo Naltrexone N = 30 males within-subject Eikemo, Biele et al, in revision 0,00 OMT N = 25 patientscomparison mothers N = 29 group in OMT comparison mothers Eikemo, Pedersen et al, in preparation

15 Can opioids make pain relief rewarding? Zubieta et al 2005, J Neurosci Solomon & Corbit 1974, Psychol Rev Leknes et al 2008, Eur J Neurosci

16 When context renders pain a safety signal Context Z=-16 Leknes et al, 2013, Pain Winston et al, 2014, J Neuroscience Berna*, Leknes* et al, in preparation Z= Opioid-dependent context effect? naloxone * placebo Control Relief context

17 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

18 What does the human μ-opioid system do? Regulates pain and distress Reward- and stressinduced pain relief (Fields) Offset analgesia *** Grill et al, 2002, J Neurophysiol; Yelle et al, 2008, J Neurosci; Derbyshire et al, 2009, Neuroimage; Martucci et al, 2012, Pain

19 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

20 The Hedonic Pharmacology team Thank you! Kongsberg sykehus

21 Bruno Laeng Lotte Thomsen Guido Biele Tor Endestad Frode Willoch Trine Hjørnevik Vigdis Vindenes Elisabeth Øiestad Liliana Bachs Johannes Gjerstad Marie Eikemo Olga Chelnokova Guro Løseth Jeppe Riegels Hedda Maurud Selma Øverland Lie Steven R Wilson Elin Johnsen Philipp Lobmaier Nicolaj Kunøe Monica Sarfi Irene Tracey Michael Lee Chantal Berna Thank you Dan-Mikael Ellingsen Håkan Olausson Johan Wessberg

22 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.