The primate locus coeruleus and effects of clonidine on opiate withdrawal

Studies of nonhuman primates suggested that the noradrenergic locus coeruleus (LC) may be involved as part of the neural substrate for a brain alarm function which includes attentiveness, arousal, anxiety, fear, terror, and the physiological correlates of these states. The studies compared the effects of electrical activation of tiny electrodes in the locus coeruleus with the effects of other agents and conditions which increased or decreased LC activity. The results suggested that the activation of the LC system is prevented by endogenous morphine-like substances and by opiates and that the opiate withdrawal syndrome is due to activation of this LC-noradrenergic system. Clonidine, which in low doses suppressed noradrenergic and LC activity, was therefore postulated to suppress opiate withdrawal signs and symptoms. The confirmation of this hypothesis in rats, monkeys and human subjects has added to the understanding of the mechanisms of opiate action and withdrawal.