Regulation of the high affinity binding sites for typical and atypical antidepressants in rat brain

We have characterized and studied the regulation of the high affinity binding sites in rat brain for a typical antidepressant (3H-imipramine) and an atypical antide-pressant (3H-mianserin). Repeated injections of imipramine for 10 to 14 days decreased the number of the binding sites for 3H-imipramine in the hippocampus but not in the cortex or cerebellum. Conversely, in the same rats the number of β-adrenergic receptor binding sites was down regulated in the cortex and cerebellum but not in the hippocampus. Available data indicates that down regulation of β-adrenergic receptors can be dissociated from the decrease in the number of imipramine binding sites. The binding sites for imipramine in hippocampal membranes were rapidly and irreversibly inactivated when the incubation temperature was raised from 0 to 37 °. Experiments using leupeptin and EGTA suggest that this temperature-induced reduction in the number of binding sites are due to an action of a Ca2+ dependent protease. Studies of the subcellular distribution indicates that 3H-imipramine binding sites are located in neurons. A destruction of serotonergic neurons by intracerebral injection of 5,7 dihydroxytryptamine led to a reduction in the number of 3H-imipramine binding sites in several brain areas examined; in contrast the number of 3H-mianserin binding sites was increased in some brain regions by the same treatment. Chronic treatment with p-Cl-phenylalanine increased the number of sites for mianserin but not for imipramine. Thus in serotonergic synapses, imipramine binding sites are in part located pre-synaptically whereas mianserin binding sites are in part located post-synaptically. © 1982.