IMPAIRMENT OF BLOOD-BRAIN-BARRIER FUNCTION BY SEROTONIN INDUCES DESYNCHRONIZATION OF SPONTANEOUS CEREBRAL CORTICAL ACTIVITY - EXPERIMENTAL-OBSERVATIONS IN THE ANESTHETIZED RAT
T. Winkler et al., IMPAIRMENT OF BLOOD-BRAIN-BARRIER FUNCTION BY SEROTONIN INDUCES DESYNCHRONIZATION OF SPONTANEOUS CEREBRAL CORTICAL ACTIVITY - EXPERIMENTAL-OBSERVATIONS IN THE ANESTHETIZED RAT, Neuroscience, 68(4), 1995, pp. 1097-1104
The possibility that elevation of serotonin in the circulation, which
is found in various pathological states, influences the spontaneous ce
rebral cortical activity was examined in a rat model. The electroencep
halogram was recorded using bipolar epidural electrodes placed over th
e frontal and parietal cerebral cortex. Intravenous infusion of seroto
nin (10 mu g/kg per min for 10 min) decreased the electroencephalogram
amplitude in both frontal and parietal recordings within 4 min of inf
usion. This decrease in amplitude was reversible. Pretreatment with cy
proheptadine (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 cyprohepta
dine. 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.