The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.
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