2026-09-21 オックスフォード大学
＜関連情報＞
- https://www.ox.ac.uk/news/2026-09-23-study-sheds-new-light-on-how-ketamine-may-act-rapidly-in-the-human-brain
- https://www.cell.com/current-biology/fulltext/S0960-9822(26)01095-X
ケタミンはパブロフ型学習中の嫌悪刺激に対する手綱核の活動を減弱させる Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning
Highlights
- Expectations of aversive outcomes during Pavlovian learning engage the human habenula
- Ketamine administered 24 h prior to learning reduces habenula activity
- Reduction in habenula activity during encoding has downstream effects on memory
Summary
Ketamine is an NMDA receptor antagonist with rapid antidepressant properties when administered at a subanesthetic dose. Preclinical models indicate that a direct injection of ketamine into the lateral habenula (Hb), a small midbrain structure with an evolutionarily preserved role in aversive learning across mammals, can rapidly relieve depression-like behavior. However, there is limited evidence to explain how ketamine acts on the function of the human Hb. In a translational computational neuroscience study, 70 healthy adult volunteers were randomized in a 1:1 ratio to receive ketamine (0.5 mg/kg) or placebo (NaCl 0.9%). We used an aversive Pavlovian conditioning paradigm combined with 7-tesla functional neuroimaging to show that ketamine attenuates Hb response during aversive stimuli expectations and outcomes 24 h post-infusion. Furthermore, we present preliminary evidence suggesting that when aversive learning occurs after ketamine infusion, reduced Hb activity during the learning process may lead to downstream effects that diminish the aversive impact of negative affective memories. These findings provide translational support for ketamine’s modulation of aversive learning and Hb activity and help to refine mechanistic models of its rapid antidepressant effect.
