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Effect of some tricyclic and nontricyclic antidepressants on [3H]imipramine binding and serotonin uptake in rat cerebral cortex after prolonged treatment
Fundamental and Clinical Pharmacology
Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine [( 3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard. Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmax of the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknown.
Animals Antidepressive Agents/*pharmacology Antidepressive Agents, Tricyclic/*pharmacology Cerebral Cortex/drug effects/*metabolism Imipramine/*metabolism Male Nerve Tissue Proteins/metabolism Protein Binding Rats Rats, Inbred Strains Serotonin/*metabolism
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