α2A- but not α2B/C-adrenoceptors modulate noradrenaline release in rat locus coeruleus:: voltammetric data

In this study, we used subtype-selective antagonists to determine the subtype of alpha(2)-adrenoceptor controlling noradrenaline release in rat locus coeruleus. Noradrenaline release was measured in locus coeruleus slices using fast cyclic voltammetry at carbon fibre microelectrodes, On long stimulation trains (40 pulses, 20 Hz), the alpha(2A)-adrenoceptor selective antagonist BRL 44408 (2-[2 H-(1-methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole) at 100 nM and 1 mu M significantly increased stimulated noradrenaline release, whereas the alpha(2B/C)-selective antagonist ARC 239 (2-[2[4-(o-methoxyphenyl)piperazin-1-yl] ethyl]-4,4dimethyl-1,3-(2H,4H)-isoquinolinedione) at 50 and 500 nM had no effect. On short stimuli (20 pulses, 200 Hz), the non-specific alpha(2)-adrenoceptor agonist dexmedetomidine (10 nM) significantly decreased noradrenaline release, an effect reversed by BRL 44408 (1 mu M) but not by ARC 239 (500 nM). These data demonstrate that autoreceptor control of noradrenaline release in the locus coeruleus is mediated by alpha(2A) but not alpha(2B/C)-adrenoceptors. (C) 1999 Elsevier Science B.V. All rights reserved.