16 - Blood-Central Nervous System Barriers in Morphine Dependence and Withdrawal

Abstract

This chapter focuses on the influence of morphine withdrawals as a prominent stressor on the central nervous system (CNS) function with special emphasis on the microvascular permeability disturbances in the brain and spinal cord. It also uses the pharmacological and morphological approaches to discuss the molecular mechanisms responsible for the spontaneous withdrawal-induced blood–CNS barrier disruption and brain damage. Morphine withdrawal is associated with profound stress response, immediate early gene expression in the CNS, and alterations in neurochemical metabolism, thus, creating a possibility that stress caused by morphine withdrawal will impair blood–CNS barriers function. Experiments show that spontaneous morphine withdrawal in rats is associated with a selective and specific breakdown of the blood–brain (BB), blood–cerebrospinal fluid (BCSF), and blood–spinal cord barriers (BSCB) to Evans blue albumin, radioactive iodine, and lanthanum (La3+) tracers. 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 chapter also discusses the functional significance of these findings and the mechanisms involved.