Changes in Blood-Brain Barrier Function Associated with Conditioned Fear in Rats

Abstract

Cerebrovascular endothelial cells are joined by tight junctions and lack both fenestrae and significant vesicular activity. Thus, these cells constitute the structural basis for the blood-brain barrier (BBB), which prevents the passage of high-molecular-weight, lipid-insoluble, or charged molecules, including proteins, certain amino acids, and water, into and out of the brain. Interest in BBB research has largely focused on methods to circumvent the barrier for delivery of drugs otherwise prevented from entering the brain and on the mechanisms and consequences (e.g., brain edema) of insults which cause BBB breakdown. These insults include severe hypertension, seizure, and mechanical brain injury [1,2]. Recently, increased BBB permeability to water has been reported to occur following systemic administration of amitriptyline, an antidepressant drug which has adrenergic effects in the central nervous system [3]. This finding provided additional support for the hypothesis that the permeability of cerebrovascular endothelial cells may be regulated, at least in part, by adrenergic neurons within the central nervous system [4, 5]. Although not uncontested [6–8], the possibility that BBB permeability may be dynamically modulated by neurogenic mechanisms suggests that changes in BBB permeability may occur even in the absence of some extrinsic manipulation or severe insult. Since drugs such as amitriptyline have a powerful influence on affective states, changes in emotionality could be associated with alterations in BBB permeability.