IMPAIRMENT OF BLOOD-BRAIN-BARRIER FUNCTION BY SEROTONIN INDUCES DESYNCHRONIZATION OF SPONTANEOUS CEREBRAL CORTICAL ACTIVITY - EXPERIMENTAL-OBSERVATIONS IN THE ANESTHETIZED RAT

The possibility that elevation of serotonin in the circulation, which is found in various pathological states, influences the spontaneous cerebral cortical activity was examined in a rat model. The electroencephalogram was recorded using bipolar epidural electrodes placed over the frontal and parietal cerebral cortex. Intravenous infusion of serotonin (10 mu g/kg per min for 10 min) decreased the electroencephalogram amplitude in both frontal and parietal recordings within 4 min of infusion. This decrease in amplitude was reversible. Pretreatment with cyproheptadine (a potent serotonin(2) receptor antagonist) prevented the serotonin-induced decrease of the electroencephalogram amplitude. The blood-brain barrier permeability to Evans Blue and [I-131]sodium was increased in frontal and parietal cortex. This increase in blood-brain barrier permeability was absent in animals pretreated with cyproheptadine. These results provide direct evidence that an elevated level of serotonin in blood has the capacity to influence spontaneous cortical electrical activity. This effect of serotonin on electroencephalogram appears to be due to its ability to enter into the brain parenchyma by inducing a short-term breakdown of the blood-brain barrier, probably via serotonin(2) receptors.