Release of neurotransmitters in the locus coeruleus

In the past 15 years the release of neurotransmitters and their metabolites in the locus coeruleus (LC) has been studied by using three approaches: microdialysis; push-pull superfusion; and voltammetry. These sophisticated techniques, which render it possible to follow the time course and magnitude of neurochemical changes in anaesthetized and conscious animals, have permitted great strides towards understanding neurotransmission in the LC. It appears that noradrenaline, known to be released in distant terminal fields, is also released in the somatodendritic area of LC neurons in response to drugs and physiological stimuli. Furthermore, determination of in vivo release enables the identification of functionally important neurotransmitter systems involved in relaying and integrating information reaching the LC via afferent neurons. As outlined in this review, the release rates of glutamate, aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine and catecholamines, are modified in particular by arousing and stressful stimuli, pain, changes in cardiovascular homeostasis, as well as during opioid withdrawal or the sleep-wake-cycle. Profound interactions also occur between some of the neurotransmitters released during these situations. It appears that individual stimuli produce distinct neurochemical changes which contribute to the regulation of neuronal LC activity. Stimuli that activate LC neurons, such as pain, fall of blood pressure, noise, opiate withdrawal, do not produce a uniform response but modality-specific release patterns of excitatory and inhibitory neurotransmitters within the LC. From these studies and from existing neuroanatomical and electrophysiological data our knowledge of how neurotransmitters work in concert to regulate the functional state of LC noradrenergic perikarya in physiological and pathophysiological conditions is just emerging.