Alpha2A- but not alpha2B/C-adrenoceptors modulate noradrenaline release in rat locus coeruleus: voltammetric data

In this study, we used subtype-selective antagonists to determine the subtype of alpha2-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 alpha2A-adrenoceptor selective antagonist BRL 44408 (2-[2H-(1-methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole) at 100 nM and 1 microM significantly increased stimulated noradrenaline release, whereas the alpha2B/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 alpha2-adrenoceptor agonist dexmedetomidine (10 nM) significantly decreased noradrenaline release, an effect reversed by BRL 44408 (1 microM) but not by ARC 239 (500 nM). These data demonstrate that autoreceptor control of noradrenaline release in the locus coeruleus is mediated by alpha2A but not alpha2B/C-adrenoceptors.