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

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT02557984

Collaborator

(none)

121

Enrollment

Location

Arms

1.9

Duration (Months)

62.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Addiction	Drug: Placebo Drug: Amisulpride Drug: Naltrexone	N/A

Detailed Description

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Official Title:

Dopamine D2/3- and μ-opioid Receptor Antagonists Reduce Cue-induced Reward Responding and Reward Impulsivity in Healthy Volunteers

Study Start Date :

Feb 1, 2014

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo Pill	Drug: Placebo Placebo Pill Other Names: Lactose Placebo Pill
Experimental: Amisulpride 400 mg Amisulpride (Solian®)	Drug: Amisulpride 400 mg Amisulpride Other Names: Solian
Experimental: Naltrexone 50 mg Naltrexone (Naltrexin®)	Drug: Naltrexone 50 mg Naltrexone Other Names: Naltrexin

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo Pill

Drug: Placebo

Placebo Pill

Other Names:

Lactose Placebo Pill

Experimental: Amisulpride

400 mg Amisulpride (Solian®)

Drug: Amisulpride

400 mg Amisulpride

Other Names:

Solian

Experimental: Naltrexone

50 mg Naltrexone (Naltrexin®)

Drug: Naltrexone

50 mg Naltrexone

Other Names:

Naltrexin

Outcome Measures

Primary Outcome Measures

Cue-Induced Reward Responding Measure [1 day]
Measured using a Pavlovian-to-Instrumental Transfer Task
Reward Impulsivity Measure [1 day]
Measured using a Delay Discounting Task

Secondary Outcome Measures

Mood [1 day]
Current Mood assessed by Visual Analog Scale (VAS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital	Zurich		Switzerland	8091

Sponsors and Collaborators

University of Zurich

Investigators

Principal Investigator: Boris B Quednow, Prof, University Hospital of Psychiatry Zurich
Principal Investigator: Philippe N Tobler, Prof, Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich