alpha(2)-Adrenoceptor involvement in the in vitro inhibitory effect of citalopram on a subpopulation of rat locus coeruleus neurons

Abstract

The aim of the present study was to investigate the modulation of locus coeruleus neurons by the selective serotonin (5-HT) reuptake inhibitor citalopram using single-unit extracellular recordings in rat brain slices. Citalopram inhibited the activity of a subpopulation of locus coeruleus neurons; thus 10 microM citalopram inhibited neurons by 53+/-17% (5 out of 15 cells), whereas the inhibition due to 100 microM was 64+/-4% (32 out of 42 cells). This effect was partially reversed (47+/-11%) by the alpha(2)-adrenoceptor antagonist idazoxan (10 microM), whereas it was unaffected by antagonists for 5-HT(1A), 5-HT(2,) and 5-HT(3) receptors, and mu opioid receptors. 5-HT (50 or 200 microM), the 5-HT(1A) receptor agonist 8-OH-DPAT (+/-)-8-hydroxy-2-(DI-n-propyl-amino) tetralin hydrobromide, 10 microM) and the 5-HT(2) receptor agonist DOI ([+/-]-2,5-dimetoxy-4-iodoamphetamine) hydrochloride, 10 or 30 microM) also inhibited a subpopulation of locus coeruleus cells. In addition, citalopram but not 5-HT, enhanced by 1.7 fold the inhibitory effect of noradrenaline. Long-term treatment with citalopram (20 mg/kg/day) did not modify the effect of noradrenaline and bromoxidine. Taken together, our results indicate that citalopram exerts an inhibitory effect on locus coeruleus noradrenergic neurons. alpha(2)-adrenoceptor activation may underlie this effect as a result of elevated levels of noradrenaline in the synaptic cleft.