Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-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 continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus 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 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.