CYCLIC-AMP AND INOSITOL PHOSPHATE ACCUMULATIONS IN RAT-BRAIN CORTICALSLICES FOLLOWING CHRONIC CITALOPRAM OR DESIPRAMINE ADMINISTRATION

The influence of chronic administration of desipramine (16mg/kg per da y for 8 days) or citalopram (1 mg/kg per day for 8 days) on the seroto nergic and noradrenergic stimulations of phosphoinositide hydrolysis a nd cyclic AMP formation was investigated in rat cerebral cortical slic es. This was done by means of a prelabelling method allowing the simul taneous measurement of the accumulations of (H-3) inositol phosphates ((H-3)IP) and of (C-14) cyclic AMP. Our results show that neither oi t he two drugs altered the inhibition of adenylate cyclase activity indu ced by serotonin(1) (5-HT1) receptor agonists nor did they alter 5-HT1 A and 5-HT1B receptor densities. Similarly they did not modify the sti mulation oi the inositol phosphate metabolism induced by 5-HT or norep inephrine (NE). Desipramine treatment decreased both beta-adrenoceptor -elicited cyclic AMP accumulation (-37%) and beta-adrenoceptor density (-29%), whereas citalopram was without effect, These results reinforc e the idea that the ability of antidepressants to decrease the activit y of the beta-adrenoceptor-adenylate cyclase complex is not common to ail antidepressants, and provide no evidence for the involvement of 5- HT1A and/or 5-HT1B in the mechanism of action oi these drugs.