Use of specific brain lesions to study the site of action of antidepressants

We have shown that the binding sites for typical antidepressants such as imipramine and atypical antidepressants such as mianserin are not located exclusively in serotonergic synapses. To study the mechanisms involved we have decided to use the hippocampus as a model because of the possibility to elicit surgical lesion of specific pathways. Repeated treatment of rats with desipramine decreased the density of β-adrenergic receptors in the hippocampus and cortex. This receptor down regulation was prevented by lesioning the serotonin neurons with an intracerebral injection of 5,7 dihydroxytryptamine. Unilateral transection of the fimbria-fornix led to a reduction in the number of imipramine binding sites in the deafferented side of the hippocampus. Conversely, the number of the binding sites for mianserin was increased by this lesion. Intrahippocampal injection of kainic acid brought about a reduction in the number of mianserin recognition sites leaving intact the number of imipramine recognition sites. Therefore our present results are consistent with the hypothesis that imipramine and mianserin recognition sites are located in different synapses. However these synapses are functionally related because they appear to be located in a neuronal system that operates in connecting and functionally integrating serotonergic and adrenergic nerve terminals. © 1982.