Blood-Central Nervous System Barriers in Morphine Dependence and Withdrawal

Abstract

The status of blood-central nervous system barriers during morphine dependence or withdrawal is still unknown. Morphine withdrawal is associated with profound stress response, immediate early gene expression in the CNS and alterations in neurochemical metabolism. Thus, a possibility exists that stress caused by morphine withdrawal will impair blood-CNS barriers function. Experiments carried out in our laboratory show that spontaneous morphine withdrawal in rats is associated with a selective and specific breakdown of the blood-brain, blood-CSF and blood-spinal cord barriers to Evans blue albumin, radioactive iodine and lanthanum (La3+) tracers. Several brain regions show pronounced structural alterations during morphine dependence and withdrawal. Pharmacological manipulations of nitric oxide (NO), serotonin (5-hydroxytryptamine) or Ca2+ channel during morphine dependence and withdrawal attenuates the blood-CNS barrier dysfunction and structural changes. These observations suggest that morphine dependence and withdrawal is associated with alterations in CNS microfluid environment and cellular damage. The functional significance of these findings and the probable mechanisms are discussed. © 2004 Elsevier Inc. All rights reserved.