期刊
EUROPEAN NEUROPSYCHOPHARMACOLOGY
卷 19, 期 8, 页码 571-580出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2009.02.004
关键词
Amphetamine; Antipsychotic; Dopamine; Glycine; NMDA; Schizophrenia
资金
- Laboratory of Behaviourat Neurobiology [SSR504734]
The specific gtycine transporter 1 (GlyT1) inhibitor, SSR504734, is highly effective in enhancing N-methyl-D-aspartate receptor (NMDAR) function by elevating the availability of the NMDAR co-agonist, gtycine, in the vicinity of NMDAR-containing glutamatergic synapses. According to the glutamatergic hypofunction hypothesis of schizophrenia, SSR504734 may therefore possess antipsychotic potential. Here, we evaluated the effects of SSR504734 in response to three psychomimetic drugs: phencyclidine, amphetamine, and apomorphine in mate C57BL/6 mice. SSR504734 attenuated phencyclidine-induced (5 mg/kg, i.p.) hyperlocomotion, but potentiated the motor stimulant and motor depressant effects of amphetamine (2.5 mg/kg, i.p.) and apomorphine (0.75 mg/kg, s.c.), respectively. Hence, SSR504734 not only confers resistance to NMDAR blockade, but also enhances the locomotor response to dopaminergic stimulation. The latter finding adds to reports that SSR504734 may modulate dopamine-mediated behaviour by interference with normal glutamate-dopamine interaction. The specificity of this action of SSR504734 wilt be highly relevant to its potential application as an antipsychotic agent. (C) 2009 Elsevier B.V. and ECNR.All rights reserved.
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