Down Regulation of Cerebral Cortical ³H Imipramine Binding Sites During Chronic Antidepressant Treatment is Independent of the Central Serotonergic Innervation

Abstract

The effects of chronic antidepressant (AD) administration (amitryptiline 12 mg/Kg i.p., 20 days) on cerebral cortical [³H] imipramine binding sites were examined in control rats and in serotonergic denervated animals. Both treatments independently reduced the density of [³H] imipramine binding sites by 33–40%. animals submitted to both treatments showed a slightly higher decrease in the Bmax (-50%). No alterations were observed in the apparent dissociation constant. Preincubation of cerebral cortical synaptosomal membranes with Triton X-100 (0.2% v/v), which preferentially dissolves the presynaptic component of the synaptosomes, reduced by 40% the maximal number of [³H] imipramine binding sites in control rats. In chronic AD treated rats or in serotonergic lesioned rats, membranes preincubated with Triton X-100 showed a 30% decrease in the number of [³H] imipramine sites in comparison to the sham group. The combination of both treatments produced an even larger decrease in the density of [³H] imipramine binding sites in Triton X-100 treated membranes (-55%) compared to the sham group. Taken together, these results strongly suggest that cerebral cortical [³H] imipramine binding sites