ACTIONS OF THE HYPNOTIC ANESTHETIC, DEXMEDETOMIDINE, ON NORADRENALINE RELEASE AND CELL FIRING IN RAT LOCUS-CERULEUS SLICES

We have examined the effects of the highly selective alpha2-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 alpha2 antagonist, atipamezole 10(-6) mol litre-1. These results suggest that cell firing and noradrenaline release are under alpha2 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 alpha2 agonists.