Evidence that chronic administration of paroxetine or fluoxetine enhances 5-HT2 receptor function in the brain of the guinea pig.
The effects of chronic treatment with antidepressants on 5-HT-stimulated hydrolysis of phosphoinositide (PI) in the cerebral cortex of the guinea pig were examined. The pharmacological profile of the response was consistent with it being mediated by a 5-HT2 receptor. Chronic (but not acute) treatment with the selective 5-HT uptake inhibitors, paroxetine and fluoxetine (10 mg/kg, p.o., for 21 days), resulted in a significant increase in the maximum response to 5-HT without altering the EC50. There were no significant alterations in the density or affinity of 5-HT2 receptors, labelled with [3H]ketanserin. In contrast, treatment with the tricyclic antidepressant, amitriptyline (10 mg/kg, p.o., for 21 days), did not produce a significant change in 5-HT-stimulated hydrolysis of PI or in the number and affinity of 5-HT2 receptors. The findings are discussed in relation to the possible neurochemical targets for antidepressant drugs and species differences in the responses to these agents.
Cadogan
A K
AK
Department of Physiology and Pharmacology, Medical School, Queens Medical Centre, Nottingham, U.K.
Marsden
C A
CA
Tulloch
I
I
Kendall
D A
DA
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D000639:Amitriptyline; D012701:Serotonin; D000001:Calcimycin; D017374:Paroxetine; D007294:Inositol; D007650:Ketanserin; D002118:Calcium