Effect of D-amphetamine on Reward Functioning

The University of Texas Health Science Center, Houston68 enrolled

Overview

The purpose of this study is to establish the dose-response curve for therapeutic doses of d-amphetamine on tasks of motivation and reward learning in the same participants and to use d-amphetamine as a dopaminergic probe to test newer theories about the role of dopamine in reward-related decision-making.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Anhedonia

Interventions

10 mg d-amphetamineDRUG

10 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.

20mg d-amphetamineDRUG

20 mg d-amphetamine dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.

PlaceboDRUG

Placebo dose given (double-blind) and behavioral tasks (EEfRT, PRT, ELT, CGT) administered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: \- Healthy individuals Exclusion Criteria: * Individuals with a body mass index (BMI) \<19 or \>26, as this alters dosing requirements * Individuals with high blood pressure, abnormal Electrocardiography (EKG), any medical condition requiring regular medication (except birth control), any other regular use of a drug or supplement with potentially hazardous interactions with d-amphetamine (e.g. St. John's wort), or any other medical contraindication to amphetamine administration as determined by our study physician * Individuals who report no prior experience with recreational drugs of any kind (including alcohol), or who report a previous adverse reaction to amphetamine * Individuals with a current Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) Axis I diagnosis, excluding mild Substance Use Disorders (≤ 3 symptoms) * Individuals with a lifetime history of moderate to severe Substance Use Disorder (≥ 4 symptoms), mania or psychosis. * Women who are pregnant. * individuals smoking more than 10 cigarettes per week will also be excluded, to avoid confounding the effects of nicotine withdrawal with the effects of the study drugs/procedures, as participants will not be allowed to smoke during the sessions. * individuals with less than a high-school level of education or fluency in English will be excluded as our questionnaires require high-school level fluency in English, and have not been translated and validated in other languages.

Locations (1)

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Outcomes

Primary Outcomes

Reward motivation as assessed by the Effort Expenditure for Reward Task (EEfRT)

A measure of effort-based decision-making in humans, the Effort Expenditure for Reward Task (EEfRT), will be used. The EEfRT requires participants to choose between a low-effort, low reward task vs a high-effort, high reward task. Willingness to exert effort, or reward motivation, is measured by taking the average number of hard task choices from the first 50 trials.

Time frame: about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session

Reward learning as assessed by the Probabilistic Reward Task (PRT)

The Probabilistic Reward Task (PRT), which uses a signal detection paradigm, will be used to measure response bias towards rewarded stimuli.

Time frame: about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study session

Secondary Outcomes

Reward learning as assessed by the Effort Learning Task (ELT)

The novel Effort Learning Task (ELT) will be used, in which participants learn to associate abstract shapes with reward, loss, high effort and low effort outcomes, to examine the effect of dopaminergic stimulation on reward learning. Learning rates are determined for each symbol, and trial-wise learning curves are calculated as metrics of reward learning.

Time frame: about 100 minutes to 140 minutes after receiving drug at 1st, 2nd, and 3rd study sessions

Level of influence of counterfactual information on later decision-making, as measured by the Counterfactual Gambling Task (CGT)

Striatal dopamine is involved in signalling counterfactual information, i.e. encoding differences between the value of actual outcomes and hypothetical outcomes of alternative choices. The CGT is a gambling task used to assess the relationship between choice factors (available options, expected value, and outcomes) on self-reported measures of momentary happiness and regret. Participants complete a gambling task and are informed of their outcome and of the counterfactual outcome (i.e. hypothetical outcome had the participant selected another option). With this task, the degree to which participants make choices to avoid potential regret can be estimated.

Data from ClinicalTrials.gov

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