Determination of the somatodendritic alpha2-adrenoceptor subtype located in rat locus coeruleus that modulates cortical noradrenaline release in vivo.

The regulation of extracellular noradrenaline levels in the cingulate cortex by somatodendritic alpha2-adrenoceptors located in the locus coeruleus was evaluated in the rat by using dual-probe microdialysis. The concentration of noradrenaline in the cingulate cortex was decreased (37%-40%) by administration into the locus coeruleus (1microM) of the agonists clonidine and UK14304 (bromoxidine), whereas it was increased by similar administration of the nonselective antagonist RX821002 (2-methoxyidazoxan) (+ 103%) and the selective alpha2A-adrenoceptor antagonist BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole) (+ 148%). The selective alpha2B/C-adrenoceptor antagonist ARC239 (2-[2[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl-1,3-(2 H,4H)-isoquinolimedione) did not induce changes. In the presence of BRL44408, the effects of clonidine and UK14304 were abolished, but they were not modified in the presence of ARC239. The data demonstrate that noradrenaline release in terminal areas is tonically modulated by somatodendritic alpha2A-adrenoceptors.