The acute effects of a single dose (10 mg) of selegiline on emotional and reward processing in healthy volunteers

Thesis

Rationale: One-third of patients with major depression are resistant to treatments aimed at negative affect, a resistance that correlates with the presence of anhedonia. Since anhedonia is tightly linked to dopaminergic dysfunction, low-dose selegiline (a selective MAO-B inhibitor that boosts extracellular dopamine) has been proposed as an alternative route to restore reward processing.

Aim: To determine whether a single oral 10 mg dose of selegiline acutely modulates behavioural indices of reward and emotional processing in healthy volunteers.

Methods: In a double-blind, randomised, parallel-group design, 22 adults (18–40 y) received selegiline or matched placebo and completed a battery one hour post-dose: Probabilistic Instrumental Learning Task (PILT), Effort Expenditure for Reward Task (EEfRT), a taste-reward paradigm (pre/post), and three emotional tasks (FERT, ECAT, EREC) . Exploratory analyses (α = 0.10) were necessary given modest and variable task-wise sample sizes (n = 16–22).

Key Findings: Anticipation – Selegiline blunted the fall in anticipated pleasantness for sweet taste relative to placebo (trend p ≈ 0.08) , suggesting preserved reward anticipation. Reward learning/sensitivity – In PILT, the drug slowed and dampened acquisition of reward bias for both win and loss trials, indicating impaired credit assignment. EEfRT showed no drug effect on willingness to work for reward. Emotional bias – On EREC, selegiline produced a trend toward enhanced recall of positively valenced words (p ≈ 0.09) and increased mislabelling of faces as happy on FERT, consistent with a shift toward positive emotional processing.

A single 10 mg dose of selegiline exerts a mixed, domain-specific profile: it appears to enhance anticipatory reward value and tilt emotional memory toward positivity, yet simultaneously disrupts rapid reinforcement learning. These divergent acute effects map onto distinct dopamine-dependent computations and echo prior work with other dopaminergic agents.

Limitations: The study is underpowered, uses an exploratory α, and relies solely on behavioural read-outs; noise and task design likely mask subtler effects. Larger, neuroimaging-coupled trials and, ultimately, studies in anhedonic or treatment-resistant patients are required before positioning low-dose selegiline as a pragmatic antidepressant tool.

Authors: Karaarslan, L

• DOI: 10.5287/ora-zg2yrndqq
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Keywords: depression; reward; emotion; anhedonia; selegiline; dopamine
• Subjects: experimental psychology; psychopharmacology; Psychology; Stereotyped behavior (Psychiatry)