DOWN-REGULATION OF CORTICAL BETA-ADRENOCEPTORS BY CHRONIC TREATMENT WITH FUNCTIONAL NMDA ANTAGONISTS

Down-regulation of cortical beta-adrenoceptors is observed in laboratory animals following chronic treatment with many clinically effective antidepressant therapies. [H-3]Dihydroalprenolol (DHA) binding to cortical beta-adrenoceptors was examined in mice treated with the functional NMDA antagonists 1-aminocyclopropanecarboxylic acid (ACPC) and MK-801. ACPC and MK-801 reduced [H-3]DHA binding by 19 (P < 0.05) and 21% (P < 0.05), respectively, while imipramine produced a 23% (P < 0.05) reduction. No corresponding changes in the KD Of [H-3]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.