Determination of the somatodendritic α2-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 alpha(2)-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 (1 mu M) 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 alpha(2A)-adrenaceptor antagonist BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole) (+ 148%). The selective alpha(2B/C)-adrenoceptor antagonist ARC239 (2-[2[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolinedione) 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 alpha(2A)-adrenoceptors. (C) 1999 Elsevier Science B.V. All rights reserved.