caa a22 4500 469120940 CHVBK 20180323133138.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF02245261 doi (NATIONALLICENCE)springer-10.1007/BF02245261 Chronic treatment with 1-aminocyclopropanecarboxylic acid desensitizes behavioral responses to compounds acting at the N-methyl- d -aspartate receptor complex [Elektronische Daten] [Phil Skolnick, Rachel Miller, Andrew Young, Kathleen Boje, Ramon Trullas] Functional antagonists at the N-methyl-d-aspartate (NMDA) receptor complex produce anti-depressant-like actions in preclinical models. Thus, an injection of a glycine partial agonist (1-aminocyclopropanecarboxylic acid; ACPC), a competitive NMDA antagonist (2-amino-7-phosphonoheptanoic acid; AP-7) or a use-dependent cation channel blocker (MK-801) reduced immobility in the forced swim test (FST) with efficacies comparable to imipramine (Trullas and Skolnick 1990). Seven daily injections of ACPC (200-400 mg/kg) abolished the effects of both this compound (200-1200 mg/kg) and AP-7 (200-300 mg/kg) in the FST. The loss in effectiveness of ACPC required 7 days of treatment to become fully manifest, and was reversed by discontinuing treatment. Other agents active in the FST (e.g. MK-801, imipramine, and nifedipine) were unaffected by this regimen. Moreover, ACPC and AP-7 remained active in the FST following repeated injections of MK-801, AP-7, or imipramine. Chronic treatment with ACPC did not affect its actions in the elevated plus-maze, but significantly attenuated the convulsant and lethal effects of NMDA (125 mg/kg). Tissue levels of ACPC indicate the modified behavioral responses produced by chronic treatment are not attributable to pharmacokinetic factors. These findings suggest repeated administration of ACPC may effect an "uncoupling” of NMDA and glycine receptors, resulting in an apparent desensitization of the behavioral actions of substances acting at these sites. Springer-Verlag, 1992 Glycine nationallicence 1-Aminocyclopropanecarboxylic acid nationallicence MK-801 nationallicence N-methyl- d -aspartate nationallicence Forced swim test nationallicence Skolnick Phil Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut Miller Rachel Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut Young Andrew Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut Boje Kathleen Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut Trullas Ramon Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut Psychopharmacology Springer-Verlag 107/4(1992-06-01), 489-496 0033-3158 107:4<489 1992 107 213 https://doi.org/10.1007/BF02245261 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245261 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Skolnick Phil Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Miller Rachel Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Young Andrew Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Boje Kathleen Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Trullas Ramon Laboratory of Neuroscience, NIDDK, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 107/4(1992-06-01), 489-496 0033-3158 107:4<489 1992 107 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer