Actions of the hypnotic anaesthetic, dexmedetomidine, on noradrenaline release and cell firing in rat locus coeruleus slices.

We have examined the effects of the highly selective alpha 2-adrenoceptor agonist, dexmedetomidine, on noradrenaline release and cell firing in isolated, superfused slices of rat locus coeruleus. Dexmedetomidine decreased both noradrenaline release and cell firing rate in a concentration-dependent fashion, with an EC50 of 3.97 (SEM 0.97) x 10(-9) mol litre-1 for noradrenaline release and 0.92 (0.53) x 10(-9) mol litre-1 for unit activity. Both effects were reversed completely by the selective alpha 2 antagonist, atipamezole 10(-6) mol litre-1. These results suggest that cell firing and noradrenaline release are under alpha 2 receptor control and that dexmedetomidine potently stimulates these receptors. We conclude that these effects are consistent with the locus coeruleus being a major site of action of the hypnotic anaesthetic alpha 2 agonists.