Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning.
Erdem Pulcu, Sara Costi, Pilar Artiach-Hortelano et al.
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In 30 seconds
In a randomized, placebo-controlled translational study, 70 healthy adults received ketamine (0.5 mg/kg) or placebo (NaCl 0.9%) and completed an aversive Pavlovian conditioning task during 7-tesla functional neuroimaging. At 24 h post-infusion, ketamine attenuated habenula responses to aversive stimulus expectations and outcomes. The authors also report preliminary evidence that reduced habenula activity during learning after ketamine may lessen the aversive impact of negative affective memories. The findings support a role for habenula modulation in ketamine’s effects on aversive learning, but do not establish clinical antidepressant efficacy in this healthy-volunteer study.
Key findings
- At 24 h post-infusion, ketamine attenuated habenula responses during aversive stimulus expectations and outcomes.
- Preliminary evidence linked reduced habenula activity during post-infusion aversive learning with diminished aversive impact of negative affective memories.
Why it matters
The study offers human neuroimaging evidence that ketamine can modulate habenula activity during aversive learning, a process relevant to models of its rapid antidepressant effects. This helps refine mechanistic hypotheses, while the healthy-volunteer population and preliminary memory findings mean the results should not be taken as evidence of treatment benefit in people with depression.
What to keep in mind
Participants were healthy adults, so the findings do not establish effects in patients with depression. The proposed downstream effect on negative affective memories is described as preliminary.