N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.
Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Jen-Cheng
JC
Lin
Institute of Neuroscience, National Chengchi University, 64, Sec. 2, Zhinan Road, Wenshan District, Taipei 11605, Taiwan; Research Center for Mind, Brain, and Learning, National Chengchi University, 64, Sec. 2, Zhinan Road, Wenshan District, Taipei 11605, Taiwan.
Ming-Huan
MH
Chan
Department of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan.
Mei-Yi
MY
Lee
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; School of Medicine, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan; Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. Electronic address: yichyanc@gmail.com.
Yi-Chyan
YC
Chen
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Institute of Neuroscience, National Chengchi University, 64, Sec. 2, Zhinan Road, Wenshan District, Taipei 11605, Taiwan; Department of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan. Electronic address: hwei@nhri.org.tw.
Hwei-Hsien
HH
Chen
D000161:Acoustic Stimulation; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D046353:Immobility Response, Tonic / Q000187:drug effects; D007649:Ketamine / Q000009:adverse effects* / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D065808:Prepulse Inhibition / Q000187:drug effects; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; C025138:dimethylglycine; D012521:Sarcosine
Anesthesia; Forced swimming; Glycine; NMDA receptor; Prepulse inhibition