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Web End = Psychopharmacology (2016) 233:32233235 DOI 10.1007/s00213-016-4359-x
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Web End = ORIGINAL INVESTIGATION
Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice
Jen-Cheng Lin1 & Mei-Yi Lee2 & Ming-Huan Chan4,5 & Yi-Chyan Chen1,3,6 &
Hwei-Hsien Chen1,2,4,7
Received: 14 December 2015 /Accepted: 13 June 2016 /Published online: 30 June 2016 # Springer-Verlag Berlin Heidelberg 2016
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.
Keywords Behavior . NMDA receptor . Depression . Schizophrenia . Prepulse inhibition
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00213-016-4359-x
Web End =10.1007/s00213-016-4359- x) contains supplementary material, which is available to authorized users.
* Yi-Chyan Chen [email protected]
* Hwei-Hsien Chen [email protected]
1 Graduate Institute of Medical Sciences, National Defense MedicalCenter, 161, Section 6, Minquan East. Road., Neihu District, Taipei 11453, Taiwan
2 Department of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
3 School of Medicine, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan