Inhibition of 5-hydroxytryptamine reuptake by the antidepressant citalopram in the locus coeruleus modulates the rat brain noradrenergic transmissionin vivo

The in vivo effect of the serotonin (5-HT) reuptake inhibitor antidepressan t citalopram, administered in the locus coeruleus (LC), on noradrenergic tr ansmission was evaluated in the rat brain. In dual-probe microdialysis assa ys, citalopram (0.1-100 mu M), in a concentration-dependent manner, increas ed extracellular noradrenaline (NA) in the LC and simultaneously decreased extracellular NA in the cingulate cortex (Cg). These effects of citalopram were abolished by pretreatment with the 5-HT synthesis inhibitor p-chloroph enylalanine (400 mg/kg, i.p.). When the alpha(2)-adrenoceptor antagonist RS 79948 (1 mu M) was perfused in the LC, local citalopram increased NA dialys ate in the LC but no longer modified NA dialysate in the Cg. In electrophys iological experiments, the administration of citalopram (100 mu M) in the L C by reversal dialysis, decreased the firing rate of LC neurones. The resul ts demonstrate in vivo that local administration of citalopram in the LC le ads to a decreased release of NA in the Cg. This modulation seems to be the result of an increase in NA concentration in the LC and the subsequent inh ibition of LC neurones via alpha(2)-adrenoceptors. The effects of citalopra m are dependent on the presence of endogenous 5-HT in the LC. (C) 2000 Else vier Science Ltd. All rights reserved.