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NMDA Receptors and Affective Disorders

  • Chapter
Antidepressants

Part of the book series: Contemporary Neuroscience ((CNEURO))

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Abstract

Recent in vivo and ex vivo findings indicate that the N-methyl-d-aspartate receptor complex may be a locus of antidepressant action (see Chapters 6 and 7). Functional antagonists of the NMDA receptor complex, including a competitive NMDA antagonist (2-amino-7-phosphonoheptanoic acid [AP-7] (1), a glycine partial agonist (1-aminocyclopropanecarboxylic acid [ACPC] (2,3), and a use-dependent channel antagonist (dizocilpine (4), are as efficacious as tricyclic antidepressants in preclinical tests predictive of antidepressant activity (5–8). Similarly, dizocilpine and the NMDA receptor antagonist CGP-37849 block the behavioral effects of two putative animal models of depression, learned helplessness and chronic mild stress-induced deficits in sucrose consumption (9–11). Moreover, a chronic regimen of either ACPC or dizocilpine produces a reduction in the density (downregulation) of cortical β-adrenoceptors in mice comparable to that produced by the prototypic tricyclic antidepressant imipramine (12). Likewise, Klimek and Papp (13) have reported that chronic dizocilpine treatment down-regulates cortical β-adrenoceptors, as well as 5-HT2 receptor, in rats. Thus, in both behavioral and biochemical screening procedures, antagonists at the NMDA receptor complex behave in a manner comparable to clinically active antidepressants.

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Authors
  1. Ian A. Paul
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Editors and Affiliations

  1. Laboratory of Neuroscience, National Institutes of Health, Bethesda, MD, USA

    Phil Skolnick

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© 1997 Springer Science+Business Media New York

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Paul, I.A. (1997). NMDA Receptors and Affective Disorders. In: Skolnick, P. (eds) Antidepressants. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-474-0_8

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  • DOI: https://doi.org/10.1007/978-1-59259-474-0_8

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-048-9

  • Online ISBN: 978-1-59259-474-0

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