Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.
Jen-Cheng Lin, Mei-Yi Lee, Ming‐huan Chan, Yi-Chyan Chen, Hwei‐hsien Chen
Psychopharmacology September 2016 DOI: 10.1007/s00213-016-4359-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Betaine Ketamine |
| Measures | Forced swimming test, Novelty suppressed feeding test, Prepulse inhibition, Novel object recognition test, Social interaction test, Rotarod test |
| Topics | Depression Esketamine Ketamine |
| Keywords | Behavior Nmda receptor Prepulse inhibition Schizophrenia |
| Key points | Betaine combined with ketamine produced stronger antidepressant-like effects than either alone in mice, while betaine attenuated ketamine-induced psychotomimetic-like behaviors (prepulse inhibition, novel object recognition, social interaction, and rotarod impairments) but not hyperlocomotion or loss of righting reflex. The authors suggest betaine could be an add-on therapy to ketamine for treatment-resistant depression and depressive symptoms in schizophrenia. |
Abstract
Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 7
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice. Biomedicines June 25, 2023
- Ketamine retards recovery from reward downshift and supports conditioned taste aversion. Pharmacology, Biochemistry, and Behavior October 28, 2023
- Co-administration of cannabidiol and ketamine induces antidepressant-like effects devoid of hyperlocomotor side-effects. Neuropharmacology June 19, 2021
- Ketamine's schizophrenia-like effects are prevented by targeting PTP1B. Neurobiology of Disease May 17, 2021
and 2 more in the library
Cites 13
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- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression The Journal of Clinical Psychiatry September 2, 2014
- A single infusion of ketamine improves depression scores in patients with anxious bipolar depression Bipolar Disorders November 14, 2014
- Acute d-serine treatment produces antidepressant-like effects in rodents The International Journal of Neuropsychopharmacology September 12, 2011
and 8 more in the library