Clonidine and the primate locus coeruleus: evidence suggesting anxiolytic and anti-withdrawal effects

One may conclude from this series of studies and the data of others reviewed at this symposium that NE systems are involved in fear or anxiety and in mediating the actions of opioids and endorphins. It is rational pharmacotherapy, therefore, to utilize anatomically and neurophysiologically characterized receptors to produce those desired specific effects on NE systems that are expected to reduce anxiety. These same receptor interactions could also be used to antagonize side effects or to reverse withdrawal syndromes via alternative receptor sites. This strategy of using different receptors to produce synergistic or antagonistic effects on a common neuronal pathway has benefited the treatment of pathological anxiety, pain, drug withdrawal symptoms, and other classical psychosomatic conditions. It should be emphasized, of course, that the LC-noradrenergic system has a much broader function than the mediation of fear or anxiety, and that the endorphins, opiates, and clonidine influence many other systems, as do their abstinence syndromes. Anatomical projections of the LC and similar central NE systems also produce the observed effects. Detailed studies are needed to discover precisely how the abnormalities observed in numerous biochemical systems [Eidelberg, 1976] are related to the alterations in NE function we have studied and discussed in this chapter. Finally, careful clinical studies are needed to determine, define, and delimit the potential therapeutic uses of clonidine in the areas suggested by the preliminary studies reviewed here.