POTENTIATION OF BARBITURATE-INDUCED ALTERATIONS IN PRESYNAPTIC NORADRENERGIC FUNCTION IN RAT FRONTAL-CORTEX BY IMIDAZOL(IN)E ALPHA(2)-ADRENOCEPTOR AGONISTS

1 In order to resolve the extent to which presynaptic noradrenergic me chanisms contribute to the anaesthetic-sparing effects of alpha(2)-adr enoceptor agonists in vivo microdialysis was used to investigate the c ombined effects of sodium pentobarbitone and imidazol(in)e alpha(2)-ad renoceptor agonists on extracellular levels of noradrenaline (NA) in t he rat frontal cortex. 2 Dialysate levels of NA were markedly reduced by the addition of TTX (2 mu M) or by the removal of calcium in the pe rfusate. These data imply that dialysate NA. levels are ultimately dep endent on exocytotic release mechanisms from afferent coeruleo-cortica l neurones. 3 Systemic administration of sodium pentobarbitone (85 mg kg(-1), i.p.) induced general anaesthesia and reduced NA levels by 92% after 30 min. The restoration of basal levels 90 min later was closel y associated with a return of the corneal blink reflex. 4 Basal NA lev els in conscious animals were not affected by an intravenous infusion of equally radioactive solutions of either imidazoline (clonidine) or imidazole (miverazol) alpha(2)-adrenoceptor agonists. The dose rate em ployed for each compound was 2 mu g kg(-1) h(-1) over 2 h. 5 The co-ad ministration of intravenous clonidine or mivazerol: each at 2 mu g kg( -1) h(-1) for 2 h, with sodium pentobarbitone (85 mg kg(-1), i.p.), pr oduced a marked and prolonged reduction in NA efflux. After 2 h, NA le vels remained suppressed by 95% (clonidine:) and 80% (mivazerol) and a nimals remained deeply anaesthetized. 6 The accumulation of tritium in brain tissue was 42-73% lower across all brain regions examined after [H-3]-mivazerol administration than after [H-3]-clonidine administrat ion. Sodium pentobarbitone did not alter the accumulation of tritium i n brain tissue after the administration of either alpha(2)-adrenocepto r agonist. 7 These data demonstrate that alpha(2)-adrenoceptor agonist s potentiate the inhibitory effects of sodium pentobarbitone on extrac ellular levels of NA in the frontal cortex. Further studies will be ne cessary to establish a causal role of noradrenergic mechanisms in the potentiation of anaesthesia by selective alpha(2)-adrenoceptor agonist s.