Losartan and Emotional Memory
Condition: Memory; Learning
Study type: Interventional

Summary: 
      This study explores the effects of single-dose losartan (50mg) versus identical placebo
      capsule on emotional memory and learning in healthy volunteers.
    

Detailed description: 
      The commonly prescribed antihypertensive drug losartan (brand name: Cozaar; UK licensed for
      20 years) targets the renin-angiotensin system - a hormone system regulating blood pressure -
      by acting as an angiotensin receptor antagonist. In particular, the drug prevents a docking
      of the protein angiotensin IV to AT1 receptors, which leads to a dilation if vessels and a
      reduction in blood pressure. However, the increase in free angiotensin IV has also been
      associated with an increase in synaptic plasticity, the cellular mechanism involved in
      learning and memory. As such, losartan appears to have cognition-enhancing properties, in a
      way that a single dose of 50mg improves prospective memory in healthy humans. However,
      preliminary pre-clinical results also suggest that a single injection of the drug improves
      fear extinction in rodents, which is the equivalent to human cognitive-behavioural therapy
      for anxiety disorders. Furthermore, compared to other antihypertensive drugs, regular
      losartan treatment appears to prevent the development of post-traumatic stress disorder
      symptoms following trauma exposition. Such results suggest that the renin-angiotensin system
      plays a key role in the development and extinction of anxiety, and that adding losartan to
      cognitive-behavioural therapy for anxiety in humans might have synergistic effects. However,
      it remains to be clarified what the basic effects of this drug on emotional information
      processing in humans are to identify mechanisms by which it may improve psychological
      treatments.

      In this study, the key neuropsychological effects of probing the renin-angiotensin system on
      emotional information processing and learning will be investigated. In a double-blind,
      randomised between-groups design, 54 healthy volunteers will be randomised to a group
      receiving a single dose of losartan (50mg) versus placebo. When peak plasma levels are
      reached, participants will work on a battery of behavioural measures of emotional information
      processing and learning.

      The results from this study will help understand how the renin-angiotensin system affects
      emotional information processing and learning, and they will help establish a battery of
      tasks that sensitively respond to such manipulations. Such information will ultimately lead
      to the development of losartan and similar agents for the more effective and more compact
      treatment of anxiety disorders.
    

Intervention name(s): Losartan Potassium; placebo
Intervention type(s): Drug; Other
Intervention description(s): active drug; placebo
Intervention MeSH terms: Losartan
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel randomised
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: anxiety; losartan; appetitive learning; aversive learning