Cyclic AMP and inositol phosphate accumulations in rat brain cortical slices following chronic citalopram or desipramine administration.
The influence of chronic administration of desipramine (16 mg/kg per day for 8 days) or citalopram (1 mg/kg per day for 8 days) on the serotonergic and noradrenergic stimulations of phosphoinositide hydrolysis and cyclic AMP formation was investigated in rat cerebral cortical slices. This was done by means of a prelabelling method allowing the simultaneous measurement of the accumulations of (3H) inositol phosphates ((3H)IP) and of (14C) cyclic AMP. Our results show that neither of the two drugs altered the inhibition of adenylate cyclase activity induced by serotonin1 (5-HT1) receptor agonists nor did they alter 5-HT1A and 5-HT1B receptor densities. Similarly they did not modify the stimulation of the inositol phosphate metabolism induced by 5-HT or norepinephrine (NE). Desipramine treatment decreased both beta-adrenoceptor-elicited cyclic AMP accumulation (-37%) and beta-adrenoceptor density (-29%), whereas citalopram was without effect. These results reinforce the idea that the ability of antidepressants to decrease the activity of the beta-adrenoceptor-adenylate cyclase complex is not common to all antidepressants, and provide no evidence for the involvement of 5-HT1A and/or 5-HT1B in the mechanism of action of these drugs.
Department of Pharmacology, Faculty of Medicine of Paris XII, Creteil, France.
R
R
Sapena
D
D
Morin
R
R
Zini
J P
JP
Tillement
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D015283:Citalopram; D005576:Colforsin; D000242:Cyclic AMP; D003891:Desipramine; D007295:Inositol Phosphates; D009638:Norepinephrine; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013566:Sympathomimetics