Dopamine and Opioid Receptor Antagonists Reduce Cue-induced Reward Responding and Reward Impulsivity

NCT ID: NCT02557984

Last Updated: 2015-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2014-04-30

Brief Summary

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The purpose of this study is to determine how the dopamine and opioid system is involved in reward processing, specifically in cue-induced reward responding and reward impulsivity, using dopamine and opioid receptor antagonists in healthy participants. The investigators predict that particularly the dopamine challenge should alter cue-induced reward responding and reward impulsivity. Such effects would be of high interest for the treatment of disorders which involve impairments of reward processing such as addiction.

Detailed Description

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In this study the investigators use amisulpride and naltrexone to elucidate what function the dopamine and opioid system have in the processing of reward. Amisulpride \[Solian®; sanofi-aventis\] is an atypical antipsychotic and acts as an antagonist at dopamine D2 and D3 (D2/D3) receptors with very high specificity. Amisulpride has been used in numerous past studies to study the role of dopamine in the brain, for example in studies on reinforcement learning, memory, and attentional bias in stimulant dependence. Naltrexone \[Naltrexin®; OrPha Swiss GmbH\] is an opioid antagonist and is clinically used in the management of alcohol and opioid dependence. It has been used to investigate the role of opioid in pain perception, taste detection and recognition, and smoking behavior. The investigators were interested in particular how amisulpride and naltrexone influence cue-induced reward responding and reward impulsivity.

Study Aims

A) Investigating the role of the dopamine system in cue-induced reward responding; B) Investigating the role of the dopamine system in reward impulsivity; C) Investigating the role of the opioid system in cue-induced reward responding; A) Investigating the role of the opioid system in reward impulsivity.

Study Design

This is a double-blind, randomized, placebo-controlled, between-subject blocker study. 121 participants received either placebo, the dopamine D2/D3 receptor antagonist amisulpride (400 mg), or the unselective opioid receptor antagonist naltrexone (50 mg), 3h before the experimental tasks. Subjective effects on mood were assessed by visual analogue scales (VAS). Cue-induced reward responding was measured using a standard Pavlovian-to-Instrumental Transfer (PIT) task, where participants press a button for reward in the presence of a stimulus predicting that reward. Reward impulsivity was measured using a Delay Discounting (DD) Task, in which participants choose between smaller, immediate rewards and larger, delayed rewards.

Conditions

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Addiction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

Placebo Pill

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo Pill

Amisulpride

400 mg Amisulpride (Solian®)

Group Type EXPERIMENTAL

Amisulpride

Intervention Type DRUG

400 mg Amisulpride

Naltrexone

50 mg Naltrexone (Naltrexin®)

Group Type EXPERIMENTAL

Naltrexone

Intervention Type DRUG

50 mg Naltrexone

Interventions

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Placebo

Placebo Pill

Intervention Type DRUG

Amisulpride

400 mg Amisulpride

Intervention Type DRUG

Naltrexone

50 mg Naltrexone

Intervention Type DRUG

Other Intervention Names

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Lactose Placebo Pill Solian Naltrexin

Eligibility Criteria

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Inclusion Criteria

* Physically and psychiatrically healthy men and women

Exclusion Criteria

* Serious past brain disease or injury
* Pacemaker or neurostimulator
* Hearing aid
* Surgery to head or heart
* Potential metal parts in body (metal splinters, gun wounds, shrapnel or surgical clips)
* Neurological or psychiatric problems (including alcoholism, depression, schizophrenia, bipolar disorders, anxiety disorder, claustrophobia, or parkinsonian symptoms)
* High blood pressure, low blood pressure, cardiac attack in anamnesis, irregular heart rate
* Epilepsy
* Emphysema, chest problems, or multiple sclerosis
* Respiratory problems (including difficulty breathing through the nose)
* Pregnancy, nursing, or planning pregnancy
* Diabetes
* Acute Hepatitis
* Allergy or sensitivity to lactose
* Allergy or sensitivity to amisulpride or naltrexone
* Breast cancer or current tumors
* Insufficiency of liver or kidney
* Past use of opiates or other drugs that may interact with amisulpride or naltrexone (such as stimulants)
* Currently taking medications known to interact with amisulpride or naltrexone (including medicines used to treat irregular heart rhythm such as quinidine, disopyramide, amiodarone and sotalol, cisapride, antibiotics such as erythromycin and pentamidine, levodopa, thioridazone (an antipsychotic), or methadone)
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boris B Quednow, Prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Psychiatry Zurich

Philippe N Tobler, Prof

Role: PRINCIPAL_INVESTIGATOR

Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich

Locations

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University Hospital

Zurich, Canton of Zurich, Switzerland

Site Status

Countries

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Switzerland

References

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Arbisi PA, Billington CJ, Levine AS. The effect of naltrexone on taste detection and recognition threshold. Appetite. 1999 Apr;32(2):241-9. doi: 10.1006/appe.1998.0217.

Reference Type BACKGROUND
PMID: 10097028 (View on PubMed)

Gibbs AA, Naudts KH, Spencer EP, David AS. The role of dopamine in attentional and memory biases for emotional information. Am J Psychiatry. 2007 Oct;164(10):1603-9; quiz 1624. doi: 10.1176/appi.ajp.2007.06081241.

Reference Type BACKGROUND
PMID: 17898353 (View on PubMed)

Gonzalez JP, Brogden RN. Naltrexone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence. Drugs. 1988 Mar;35(3):192-213. doi: 10.2165/00003495-198835030-00002.

Reference Type BACKGROUND
PMID: 2836152 (View on PubMed)

Jocham G, Klein TA, Ullsperger M. Dopamine-mediated reinforcement learning signals in the striatum and ventromedial prefrontal cortex underlie value-based choices. J Neurosci. 2011 Feb 2;31(5):1606-13. doi: 10.1523/JNEUROSCI.3904-10.2011.

Reference Type BACKGROUND
PMID: 21289169 (View on PubMed)

Ersche KD, Bullmore ET, Craig KJ, Shabbir SS, Abbott S, Muller U, Ooi C, Suckling J, Barnes A, Sahakian BJ, Merlo-Pich EV, Robbins TW. Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence. Arch Gen Psychiatry. 2010 Jun;67(6):632-44. doi: 10.1001/archgenpsychiatry.2010.60.

Reference Type BACKGROUND
PMID: 20530013 (View on PubMed)

Morein-Zamir S, Craig KJ, Ersche KD, Abbott S, Muller U, Fineberg NA, Bullmore ET, Sahakian BJ, Robbins TW. Impaired visuospatial associative memory and attention in obsessive compulsive disorder but no evidence for differential dopaminergic modulation. Psychopharmacology (Berl). 2010 Oct;212(3):357-67. doi: 10.1007/s00213-010-1963-z. Epub 2010 Jul 27.

Reference Type BACKGROUND
PMID: 20661550 (View on PubMed)

Rukstalis M, Jepson C, Strasser A, Lynch KG, Perkins K, Patterson F, Lerman C. Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm. Psychopharmacology (Berl). 2005 Jun;180(1):41-8. doi: 10.1007/s00213-004-2136-8. Epub 2005 Jan 29.

Reference Type BACKGROUND
PMID: 15682300 (View on PubMed)

Lovibond PF, Colagiuri B. Facilitation of voluntary goal-directed action by reward cues. Psychol Sci. 2013 Oct;24(10):2030-7. doi: 10.1177/0956797613484043. Epub 2013 Aug 27.

Reference Type BACKGROUND
PMID: 23982242 (View on PubMed)

Soutschek A, Weber SC, Kahnt T, Quednow BB, Tobler PN. Opioid antagonism modulates wanting-related frontostriatal connectivity. Elife. 2021 Nov 11;10:e71077. doi: 10.7554/eLife.71077.

Reference Type DERIVED
PMID: 34761749 (View on PubMed)

Other Identifiers

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SNS_Study_01

Identifier Type: -

Identifier Source: org_study_id

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