The possibility that stress associated with
morphine administration or withdrawal will influence the blood-brain barrier (BBB) dysfunction,
brain edema formation and brain pathology was examined in a rat model. Repeated daily administration of
morphine (10 mg/kg, i.p.) resulted in
drug dependence in rats on the 6th day and onwards. The BBB permeability to
Evans blue albumin (EBA) and radioiodine ([131])
Iodine did not alter during
morphine dependence up to the 12th day. On the other hand, spontaneous withdrawal of
morphine on day 1 resulted in profound stress symptoms and breakdown of the BBB to
protein tracers in several brain regions. This increase in BBB to
protein tracers was most pronounced on the 2nd day of
morphine withdrawal. These rats also exhibited marked
brain edema and abnormal neuronal and glial cell responses. Pretreatment with an
antioxidant H-290/51 markedly attenuated the BBB dysfunction,
brain edema formation and brain pathology during
morphine withdrawal phases. These observations suggest that psychostimulants and associated oxidative stress are capable to induce brain pathology through modifying the BBB function.