Binding and function of serotonin 2 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 serotonin 2 receptors.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007099:Imipramine / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D011985:Receptors, Serotonin; D015016:Yohimbine; D006916:5-Hydroxytryptophan; D007099:Imipramine