Inhibition of striatal dopamine release by glycine and glycyldodecylamide.
Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) antagonists induce schizophrenia-like symptoms in humans. In rodents, PCP induces a syndrome of stereotypies and hyperactivity that is accompanied by stimulation of striatal dopamine release. Glycine and other NMDA agonists reverse PCP-induced behaviors in rodents and ameliorate PCP psychosis-like symptoms of schizophrenia in clinical trials. Glycine levels in vivo are regulated by the actions of glycine (GLYT1) transporters. The present study investigates effects of glycine and the prototypic glycine transport inhibitor glycyldodecylamide (GDA) on striatal dopamine release in vitro using a mouse striatal assay. Glycine and GDA significantly inhibit NMDA-induced striatal dopamine release, consistent with their ability to enhance local striatal inhibitory neurotransmission in vitro and to reverse PCP-induced hyperactivity in vivo.
Javitt
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Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. javitt@nki.rfmh.org
Sershen
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Hashim
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Lajtha
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D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D000634:Aminoquinolines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C109520:glycyldodecylamide; D014316:Tritium; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D016202:N-Methylaspartate; D010622:Phencyclidine; D005998:Glycine; D004298:Dopamine