TY - JOUR
T1 - Interactions between the glycine transporter 1(GlyT1) inhibitor SSR504734 and psychoactive drugs in mouse motor behaviour
AU - Singer, Philipp
AU - Feldon, Joram
AU - Yee, Benjamin K.
N1 - Funding Information:
Funding for the present study was provided by the Swiss Federal Institute of Technology (ETH) Zurich and the NCCR Neural Plasticity & Repair (funded by the Swiss National Science Foundation). The experimental compound SSR504734 was provided free without any contractual agreement by Sanofi Aventis (Paris, France). None of these played any further role in the design of the study, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.
PY - 2009/8
Y1 - 2009/8
N2 - The specific glycine 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, glycine, 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 male 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 will be highly relevant to its potential application as an antipsychotic agent.
AB - The specific glycine 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, glycine, 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 male 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 will be highly relevant to its potential application as an antipsychotic agent.
KW - Amphetamine;
KW - Antipsychotic;
KW - Dopamine;
KW - Glycine;
KW - NMDA;
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=67349167781&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2009.02.004
DO - 10.1016/j.euroneuro.2009.02.004
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AN - SCOPUS:67349167781
SN - 0924-977X
VL - 19
SP - 571
EP - 580
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 8
ER -
