Effect of mianserin on locomotory function after thoracic spinal cord hemisection in rats

To study the role of serotonin (5-HT) in spinal cord injury, we observed the effects of mianserin (a 5-HT1c and 5-HT2 receptor antagonist) on rat locomotory function after thoracic spinal cord hemisection. Three groups of rats were studied: sham, A, and B. The sham group (n = 4) received laminectomy and a 3-day course of mianserin (5 mg/kg ip); group A (n = 12) had laminectomy, hemisection, and weekly 3-day courses of saline or mianserin; group B (n = 12) was identical to group A except that the rats received saline. The rats were evaluated every other day for 6 weeks using a 0-14 point scale. Hemisection markedly reduced mean ipsilateral hindlimb scores from 14.0 to 4.0 +/- 0.4 and 4.6 +/- 0.2 (mean +/- standard deviation) in groups A and B, respectively. The saline-treated rats recovered to scores of 9 or 10 by Day 7, 12 or 13 by Day 14, and normal by Day 21. Mianserin significantly but transiently depressed mean locomotory scores, from 12.1 +/- 0.6 to 10.0 +/- 0.4 (P < 0.05, Mann-Whitney U test) in the second week and from 14.0 +/- 0.0 to 12.1 +/- 0.6 (P < 0.05, Mann-Whitney U test) in the fourth week after hemisection. Locomotory scores of mianserin-treated rats did not differ significantly from control saline-treated rats by 7 days after treatment. Immunohistological studies of the spinal cords revealed a marked reduction of 5-HT-containing terminals in ipsilateral but not contralateral lumbosacral cord by 2 weeks after hemisection. By 4 weeks after hemisection, 5-HT-immunoreactive fibers and terminals partly returned to the ipsilateral lumbosacral cord, corresponding temporally with locomotory recovery. Thus, 5-HT may play a role in recovery after hemisection. Anti-serotonergic drugs should be cautiously administered to patients recovering from spinal cord injury.