The Effects of the Dopamine Receptor Agonist Pramipexole on Reward and Emotion Related Information Processing in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change in reward sensitivity on a reinforcement learning task between baseline and final day of assessment
研究概览
简要总结
The dopamine agonist pramipexole has recently been suggested as a potential novel antidepressant drug. While preliminary clinical data hint at its efficacy in treating depressive symptoms, our current understanding of its impact on neurocognitive processes is relatively limited. This is in part because mechanistic studies have largely focused on the effects of single-dose treatments. However, such acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically. This study therefore aims to explore and characterise the neurocognitive effects of more prolonged pramipexole treatment. Forty healthy volunteers will be randomly allocated to 12 to 15 days of treatment with either pramipexole or placebo. Study participants as well as researchers will be blinded as to which treatment is used. Before and after treatment all participants will perform a set of psychological tasks and questionnaires evaluating reward-based learning, emotional information processing, motivational vigour and subjective experience. Furthermore, functional magnetic resonance imaging (fMRI) will be used to compare neural activity during emotion and reward processing between the two treatment groups. We hypothesises that pramipexole might enhance reward sensitivity, motivational vigour, and pleasure experience and could induce positive biases in emotional information processing.
详细描述
Background:
The dopamine receptor agonist pramipexole has recently been suggested as a potential novel antidepressant drug. While preliminary clinical data hint at its efficacy in treating depressive symptoms, our current understanding of its impact on neurocognitive processes is relatively limited. This is in part because, so far, mechanistic studies have largely focused on the effects of single-dose treatments. However acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically.
Aim of study:
To explore and characterise the effects of a 12 to 15 day regime of pramipexole on behavioural and neural measures of reward learning, emotional information processing, motivational invigoration, and subjective experience.
Methods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •Age: 18 to 45 years
- •Good physical and mental health
- •Participant is willing and able to give informed consent for participation in the study
- •Sufficient knowledge of English language to understand and complete study tasks
- •Willingness to refrain from driving, cycling, or operating heavy machinery if necessary while taking part in the study
- •Willingness to refrain from drinking while taking part in the study.
排除标准
- •Current or past psychiatric disorder (e.g. depression, bipolar disorder etc.)
- •First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
- •BMI not between 18 and 30
- •History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
- •Any severe medical condition not stabilized at the time of the experiment (e.g. cardiovascular disease, epilepsy, asthma etc.)
- •Severe heart or blood vessel disease
- •Postural hypotension
- •Any history of seizures
- •Lactose intolerance
- •Any current or past physical illness that has the potential to significantly affect mental functioning (e.g. epilepsy, hypothyroidism, Parkinson's disease, multiple sclerosis etc.)
- •Pregnant, or lactating woman
- •Sexually active woman who does not use any medically accepted method of contraception
- •Current or previous intake (last three months) of any medication that has a significant potential to affect mental functioning (e.g. benzodiazepines, antidepressants, neuroleptics etc.)
- •Any intake of recreational drugs in the last 3 months (e.g. marijuana, ecstasy etc.)
- •Regular alcohol consumption of more than 14 units a week or excessive alcohol consumption up to three days before the experiment
- •Regular smoker (> 5 cigarettes per day)
- •Excessive caffeine user (> 6 caffeinated drinks per day)
- •History of recurrent rashes or history of allergic reactions to relevant substances (pramipexole treatment, placebo treatment, taste samples)
- •Previous participation in a study using the same or similar tasks
- •Any contraindication to magnetic resonance imaging (e.g. metallic implant, severe claustrophobia)
- •Current participation in another study
- •In the researcher's opinion participation in the study could be harmful or severely distressing to the participant (e.g. intolerance of side effects) or the participant is not able to follow instructions or complete study tasks
研究组 & 干预措施
Pramipexole
Maximum daily dose: 1.0 mg of pramipexole salt
干预措施: Pramipexole (Drug)
Placebo
Lactose
干预措施: Placebo (Drug)
结局指标
主要结局
Change in reward sensitivity on a reinforcement learning task between baseline and final day of assessment
时间窗: Completed at day 12 to 15 of treatment
Participants are shown two distinct abstract shapes and have to choose one of them. On each trial, one of the two shapes is associated with a 'win' (resulting in a small monetary gain) and one with a 'loss' (resulting in a small monetary loss). The two outcomes are independent (knowing the location of the win provides no information about the location of the loss). During the task, the information content of the outcomes is manipulated independently by varying the volatility of their occurrence (three conditions: 'win volatile, loss volatile', 'win stable, loss volatile', 'win volatile, loss stable'). Using trial and error, participants have to learn the stimulus-outcome associations and use their knowledge to maximise monetary earnings. Choices are made via button-press. Choice, choice reaction time and pupillary dilation in response to outcome presentation are recorded. By fitting a computational model, reward sensitivity is estimated.
次要结局
- Change in subjective experience of pleasure(Completed at day 12 to 15 of treatment)
- Change in performance in an emotional faces dot probe task(Completed at day 12 to 15 of treatment)
- Amygdala BOLD signal in response to positive and negative emotional faces(Completed at day 12 to 15 of treatment)
- Change in performance in a probabilistic instrumental learning task(Completed at day 12 to 15 of treatment)
- Change in performance in an emotional categorisation task(Completed at day 12 to 15 of treatment)
- Change in performance in an emotional recall task(Completed at day 12 to 15 of treatment)
- BOLD signal in the ventral striatum, orbitofrontal cortex and anterior cingulate cortex in response to positive and negative outcomes in a probabilistic instrumental learning task(Completed at day 12 to 15 of treatment)
- Change in performance in a facial expression recognition task(Completed at day 12 to 15 of treatment)
- Change in performance in a motivational vigour task(Completed at day 12 to 15 of treatment)
- Subjective taste experience(Completed at day 12 to 15 of treatment)