A model for the cellular mechanisms of morphine tolerance and dependence

The Locus Coeruleus (LC) is the major noradrenergic nucleus, with approximately 30,000 neurons located on the floor of the fourth ventricle in the rostral pens. LC neurons submitted to acute exposure to morphine develop addiction ranging from acute to chronic, because of the alteration in concentration of intracellular messengers and in genetic expression of some proteins. Although the main electrophysiological effects of opiates in the LC are well established, some of the cellular mechanisms of morphine tolerance and dependence have required further research. This work contains results related to both a mathematical model that simulates the effects of morphine in a. LC neuron, and the hypothesis that only the increase in genetic expression of a protein is sufficient to allow the neuron to develop tolerance and range from acute to chronic addiction. Simulations based on the model show interesting results that allow us to infer that the hypothesis proposed is sufficient for neurons to attain chronic dependence. (C) 2000 Elsevier Science Ltd. All rights reserved.