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.
Department of Physiology and Pharmacology, Medical School, Queens Medical Centre, Nottingham, U.K.
A K
AK
Cadogan
C A
CA
Marsden
I
I
Tulloch
D A
DA
Kendall
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