Chronic treatment with opiates leads to three well-known consequences: tolerance, which is a decrease in the effect of a drug with chronic use; sensitization, which is an increase in the effect of a drug with chronic use; and physical dependence, which is a change in functioning produced by chronic use, such that absence of the drug results in an unpleasant withdrawal syndrome. These phenomena are important in both the use of opiates for the treatment of chronic pain and in the development of opiate addiction. Recent experiments suggest that excitatory amino acid systems may have an important role in the development and/or expression of these phenomena. The present studies are designed to explore the potential role of a type of excitatory amino acid receptor, the N-methyl-D-aspartate (NMDA) receptor, in opiate tolerance, sensitization and physical dependence. Adult male Sprague-Dawley rats will be treated chronically with morphine. Tolerance, sensitization and physical dependence will be studied by assessing several indices of locomotor activity. The effects of MK-801, a potent and selective NMDA receptor antagonist, will be examined on the development and expression of all three phenomena. These studies will help to determine the role of NMDA receptors in the behavioral consequences of long-term opiate administration, and may lead to better treatments for chronic pain and opiate addiction.
| Trujillo, K A (2000) Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical studies. Psychopharmacology (Berl) 151:121-41 |
