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

Study Overview
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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.

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

Conditions
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Addiction

Intervention / Treatment
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* Drug: Placebo
* Drug: Amisulpride
* Drug: Naltrexone


Participation Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Pill | Drug: Placebo<br>* Placebo Pill<br>* Other names: Lactose Placebo Pill;|
| Experimental: Amisulpride<br>400 mg Amisulpride (Solian®) | Drug: Amisulpride<br>* 400 mg Amisulpride<br>* Other names: Solian;|
| Experimental: Naltrexone<br>50 mg Naltrexone (Naltrexin®) | Drug: Naltrexone<br>* 50 mg Naltrexone<br>* Other names: Naltrexin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cue-Induced Reward Responding Measure | Measured using a Pavlovian-to-Instrumental Transfer Task | 1 day | 
| Reward Impulsivity Measure | Measured using a Delay Discounting Task | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mood | Current Mood assessed by Visual Analog Scale (VAS) | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dopamine, Opioid, Reward