PROBABLE INVOLVEMENT OF SEROTONIN IN THE INCREASED PERMEABILITY OF THE BLOOD-BRAIN-BARRIER BY FORCED SWIMMING - AN EXPERIMENTAL-STUDY USINGEVANS BLUE AND I-131 SODIUM TRACERS IN THE RAT

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to cont inuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, i ncreased the permeability of the BBB to Evans blue albumin (EBA) and I -131-sodium in six and nine brain regions, respectively. The EBA stain ing was noted in posterior cingulate cortex, parietal, occipital corti ces, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB pe rmeability to I-131-sodium was further extended to caudate nucleus, th alamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 1 80% and 250%, respectively, from the control group. Adult animals show ed only a minor increase in brain and plasma 5-HT levels. In young ani mals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomet hacin (a prostaglandin synthesis inhibitor) prevented the FS induced i ncrease in BBB permeability and 5-HT levels. Destruction of serotonerg ic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdow n of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT, receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increa sed permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an imp ortant role in the breakdown of BBB permeability in FS, (ii) this effe ct of 5-HT on BBB permeability is mediated by 5-HT, receptors, and (ii i) FS induced increase in BBB permeability is age dependent.