In vivo tonic modulation of the noradrenaline release in the rat cortex by locus coeruleus somatodendritic alpha(2)-adrenoceptors

The regulation of noradrenaline release in the rat cingulate cortex by somatodendritic alpha(2)-adrenoceptors placed in the locus coeruleus was evaluated by dual-probe microdialysis. The alpha(2)-adrenoceptor antagonists BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole), RS79948 ((8,12,13)-decahydro-3methoxy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]-naphthyridine) and RX821002 (2-methoxyidazoxan) administered by reverse dialysis into the locus coeruleus increased concentration-dependently (0.01-100 microM) noradrenaline release in the cortex (maximal effects 170+/-30%, 543+/-17%, 195+/-26%, respectively). Administration of the alpha(2)-adrenoceptor antagonist idazoxan increased at lower (0.1-10 microM) but decreased at the highest dose (100 microM) noradrenaline in the cortex. These data demonstrate that somatodendritic alpha(2)-adrenoceptors in the locus coeruleus exert an inhibitory tonic modulation on noradrenaline release in noradrenergic terminal areas.