MilliporeSigma
  • Home
  • Search Results
  • Effects of a glycine transporter-1 inhibitor and D-serine on MK-801-induced immobility in the forced swimming test in rats.

Effects of a glycine transporter-1 inhibitor and D-serine on MK-801-induced immobility in the forced swimming test in rats.

Behavioural brain research (2014-10-11)
Kazuaki Kawaura, Hiroyuki Koike, Kohnosuke Kinoshita, Daiji Kambe, Ayaka Kaku, Jun-ichi Karasawa, Shigeyuki Chaki, Hirohiko Hikichi
ABSTRACT

Glutamatergic dysfunction, particularly the hypofunction of N-methyl-D-aspartate (NMDA) receptors, is involved in the pathophysiology of schizophrenia. The positive modulation of the glycine site on the NMDA receptor has been proposed as a novel therapeutic approach for schizophrenia. However, its efficacy against negative symptoms, which are poorly managed by current medications, has not been fully addressed. In the present study, the effects of the positive modulation of the glycine site on the NMDA receptor were investigated in an animal model of negative symptoms of schizophrenia. The subchronic administration of MK-801 increased immobility in the forced swimming test in rats without affecting spontaneous locomotor activity. The increased immobility induced by MK-801 was attenuated by the atypical antipsychotic clozapine but not by either the typical antipsychotic haloperidol or the antidepressant imipramine, indicating that the increased immobility induced by subchronic treatment with MK-801 in the forced swimming test may represent a negative symptom of schizophrenia. Likewise, positive modulation of the glycine sites on the NMDA receptor using an agonist for the glycine site, D-serine, and a glycine transporter-1 inhibitor, N-[(3R)-3-([1,1'-biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine hydrochloride (NFPS), significantly reversed the increase in immobility in MK-801-treated rats without reducing the immobility time in vehicle-treated rats. The present results show that the stimulation of the NMDA receptor through the glycine site on the receptor either directly with D-serine or by blocking glycine transporter-1 attenuates the immobility elicited by the subchronic administration of MK-801 and may be potentially useful for the treatment of negative symptoms of schizophrenia.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DL-Serine, ≥98% (TLC)
Sigma-Aldrich
DL-Serine, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98% (HPLC)
Sigma-Aldrich
Formic acid solution, BioUltra, 1.0 M in H2O
Supelco
Acetonitrile, analytical standard
Sigma-Aldrich
D-Serine, ≥98% (TLC)
Sigma-Aldrich
Acetonitrile, ≥99.5%, ACS reagent
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Formic acid, ≥95%, FCC, FG
Supelco
Acetonitrile, HPLC grade, ≥99.93%
Clozapine for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles
USP
Clozapine Resolution Mixture, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
Acetonitrile, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Acetonitrile, ReagentPlus®, 99%
Sigma-Aldrich
Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%
Sigma-Aldrich
Formic acid, ACS reagent, ≥88%
Sigma-Aldrich
Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)
Sigma-Aldrich
Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Imipramine for system suitability, European Pharmacopoeia (EP) Reference Standard