Binding and function of serotonin₂ receptors following chronic administration of imipramine

Experiments were undertaken to determine whether alterations in the binding of 5-HT₂ receptors in the cerebral cortex of rat brain, induced by antidepressant drugs, are related to behavioral changes observed in response to the administration of a precursor of serotonin. Chronic (5 days), but not acute, administration of an imipramine-yohimbine combination resulted in a significant decrease in the binding of 5-HT₂ receptors in the frontal cortex and wet-dog shakes induced by 5-hydroxytryptophan (5-HTP). The decrease in the binding to 5-HT₂ receptors was due entirely to a change in the concentration of binding sites with no modification in receptor affinity. The behavioral alteration resulted from a decrease in the maximal response to 5-HTP. Further experiments revealed that chronic (5 days) administration of imipramine alone altered the behavioral response to 5-HTP without changing the binding of 5-HT₂ receptor binding and that changes in 5-HT₂ binding in the cortex were not always accompanied by an alteration in the response to 5-HTP. These results suggest a lack of correlation between the drug-induced change in 5-HT₂ binding in frontal cortex and the function of serotonin₂ receptors.