title: Down-regulation of cortical beta-adrenoceptors by chronic treatment with functional NMDA antagonists.
abstract: Down-regulation of cortical beta-adrenoceptors is observed in laboratory animals following chronic treatment with many clinically effective antidepressant therapies. [3H]Dihydroalprenolol (DHA) binding to cortical beta-adrenoceptors was examined in mice treated with the functional NMDA antagonists 1-aminocyclopropane-carboxylic acid (ACPC) and MK-801. ACPC and MK-801 reduced [3H]DHA binding by 19 (P less than 0.05) and 21% (P less than 0.05), respectively, while imipramine produced a 23% (P less than 0.05) reduction. No corresponding changes in the KD of [3H]DHA were observed. These findings are consistent with the observation that functional NMDA antagonists are active in animal models commonly used to evaluate antidepressants and may represent a novel approach to the treatment of depression.
authors.affiliation: Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: I A
authors.initials: IA
authors.lastname: Paul
authors.forename: R
authors.initials: R
authors.lastname: Trullas
authors.forename: P
authors.initials: P
authors.lastname: Skolnick
authors.forename: G
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D000596:Amino Acids; D000598:Amino Acids, Cyclic; D011943:Receptors, Adrenergic, beta; D016194:Receptors, N-Methyl-D-Aspartate; C023863:1-aminocyclopropane-1-carboxylic acid; D004082:Dihydroalprenolol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007099:Imipramine