Long-term antidepressant treatment: Alterations in cerebral capillary permeability

Abstract

Chronic treatment of rats with amitriptyline (AMI) induced a persistent increase in the diffusibility of water into the brain (E _W). This effect was observable 12 h after the last dose. AMI induces this alteration at plasma drug concentrations of 71±13 ng/ml (the therapeutic range for man is 100–250 ng/ml). Furthermore, chronic treatment potentiated the increase observed after acute drug administration and resulted in a 350% enhancement in the permeability of water across the cerebral capillary. Thus, long-term antidepressant administration can chronically influence cerebral function by affecting capillary permeability.