Ketamine Reverses Lateral Habenula Neuronal Dysfunction and Behavioral Immobility in the Forced Swim Test Following Maternal Deprivation in Late Adolescent Rats.
Ryan D Shepard, Ludovic D Langlois, Caroline A Browne, Aylar Berenji, Irwin Lucki, Fereshteh S Nugent
Frontiers in Synaptic Neuroscience 2018 DOI: 10.3389/fnsyn.2018.00039 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Late-adolescent male rats |
| Intervention | Ketamine |
| Measures | Forced swim test (FST) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Lhb Early life stress Forced swim test Intrinsic excitability Lateral habenula Maternal deprivation |
| Key findings | Maternal deprivation increased lateral habenula intrinsic excitability and bursting activity and was associated with increased forced swim test immobility in late-adolescent male rats. A single in vivo ketamine injection reversed both the early-life stress-induced LHb neuronal dysfunction and the behavioral response, an effect the authors describe as prolonged. |
Abstract
Mounting evidence suggests that the long-term effects of adverse early life stressors on vulnerability to drug addiction and mood disorders are related to dysfunction of brain monoaminergic signaling in reward circuits. Recently, there has been a growing interest in the lateral habenula (LHb) as LHb dysfunction is linked to the development of mental health disorders through monoaminergic dysregulation within brain reward/motivational circuits and may represent a critical target for novel anti-depressants, such as ketamine. Here, we show that maternal deprivation (MD), a severe early life stressor, increases LHb intrinsic excitability and LHb bursting activity, and is associated with the development of increased immobility in the forced swim test (FST) in late-adolescent male rats. A single in vivo injection of ketamine is sufficient to exert prolonged antidepressant effects through reversal of this early life stress-induced LHb neuronal dysfunction and the response in the FST. Our assessment of ketamine's long-lasting beneficial effects on reversal of MD-associated changes in LHb neuronal function and behavior highlights the critical role of the LHb in pathophysiology of depression associated with severe early life stress and in response to novel fast-acting antidepressants.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
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- BDNF Alterations in Brain Areas and the Neurocircuitry Involved in the Antidepressant Effects of Ketamine in Animal Models, Suggest the Existence of a Primary Circuit of Depression Journal of Integrative Neuroscience August 16, 2022
- Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2025
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and 1 more in the library