Depression and the Glutamate/GABA-Glutamine Cycle.
Current Neuropharmacology 2024 DOI: 10.2174/1570159X22666240815120244 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | scopolamine ketamine ECT gammahydroxybutyrate (GHB) |
| Topics | Depression |
| Keywords | Gaba Cerebral metabolic rate. Cholinergic neurotransmission Gammahydroxybutyrate Glutamate Glutamine Brain chemistry Mental health Stress response Depression treatment |
| Citations | 24 |
| Key findings | Gammahydroxybutyrate (GHB) may achieve more permanent relief from depression and act prophylactically by restoring the balance between cholinergic and monoaminergic neurotransmission, relieving REM sleep pressure, and increasing brain glutamate. |
Abstract
Many features of major depressive disorder are mirrored in rodent models of psychological stress. These models have been used to examine the relationship between the activation of the hypothalamic- pituitary axis in response to stress, the development of oxidative stress and neuroinflammation, the dominance of cholinergic neurotransmission and the associated increase in REM sleep pressure. Rodent models have also provided valuable insights into the impairment of glycolysis and brain glucose utilization by the brain under stress, the resulting decrease in brain energy production and the reduction in glutamate/GABA-glutamine cycling. The rapidly acting antidepressants, scopolamine, ketamine and ECT, all raise extracellular glutamate and scopolamine and ketamine have specifically been shown to increase glutamate/GABA-glutamine cycling in men and rodents with corresponding short-term relief of depression. The nightly use of gammahydroxybutyrate (GHB) may achieve more permanent results and may even act prophylactically to prevent the development or recurrence of depression. GHB is a GABAB agonist and restores the normal balance between cholinergic and monoaminergic neurotransmission by inhibiting cholinergic neurotransmission. It relieves REM sleep pressure. GHB's metabolism generates NADPH, a key antioxidant cofactor. Its metabolism also generates succinate, the tricarboxylic acid cycle intermediate, to provide energy to the cell and to synthesize glutamate. In both animals and man, GHB increases the level of brain glutamate.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments Proceedings of the National Academy of Sciences November 27, 2023
and 2 more in the library