Central noradrenergic neurones and the mechanism of general anaesthesia.

Central noradrenergic neurones and the mechanism of general anaesthesia Modern anaesthetics are, in the main, safe and predictable in their use, and highly ef®cient. Moreover, it could be argued that without these properties major advances in surgical practice, so often highlighted in the media, could not have taken place. However, as an example of pharmacology, the production of the anaesthetic state remains somewhat of a mystery. This mystery results from the controversies related to the existence of a unitary anaesthetic target site. From direct observation of clinical anaesthesia, this seems unlikely as different anaesthetic agents produce different`types' of anaesthesia. GABA A receptors have long been held as a unifying cellular target (with some exceptions), but others have also been suggested. In this editorial, we consider the evidence in support of a role for noradrenergic transmission as a `wiring' target for anaesthetic action. The clear role of this system in analgesia is not considered. Norepinephrine is a major central nervous system neurotransmitter in the brainstem. Noradrenergic neurones are of great importance in the regulation of a range of behaviours including the sleep±wake cycle, feeding, ther-moregulation, attention, motor activity, and growth and development. 1 In addition, there are many studies suggesting that noradrenergic system(s) may be involved in the production of thèanaesthetic state'. In the brain, the A1, A2, A5, and A7 noradrenergic clusters constituting the lateral tegmental area, project to the thalamus and hypothalamus. 2 The locus coeruleus (A6 cluster), which is distinct from the lateral tegmental area, innervates the cerebral cortex, hippocampus, cerebellum, and spinal cord. 2 The activity of locus coeruleus neurones is slow and regular during wakefulness. 3 In contrast, when an animal becomes drowsy, entering slow wave and then REM sleep, there is a decrease in discharge rate such that during REM sleep these neurones are silent. 3 Interestingly, all noradre-nergic projections to the cerebrocortex originate from the locus coeruleus. 3 The preoptic area receives input from both the locus coeruleus (A6), and the lateral tegmental group (A1, A2, A5, and A7) noradrenergic neurones. 4 In addition, neurones in the preoptic area project back to the locus coeruleus. 5 This area plays an important role in sleep or hypnosis. What is the role of noradrenergic neurones in this area? Most of the previous studies 6 suggest that norepinephrine neurones in the preoptic area may contribute to wakefulness, as direct activation or injection of norepinephrine into this area …