M. Sakai et al., Reduction in excessive muscle tone by selective depletion of serotonin in intercollicularly decerebrated rats, BRAIN RES, 860(1-2), 2000, pp. 104-111
Intercollicular decerebration in animals induces sustained facilitation of
muscle tone of the limbs and this animal model has been used to assess cent
rally acting muscle relaxants. We have examined the involvement of central
and spinal cord serotonergic pathways in the onset of excessive muscle tone
in an intercollicularly decerebrated rat. Descending serotonergic pathways
are known to modulate, directly or indirectly, the excitability of spinal
cord motoneurons and it is inferred that serotonin (5-HT) plays an importan
t rot in locomotion. Alteration of muscle tone has been investigated in 5-H
T-depleted rats with a neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) after
pretreatment with desipramine. Intracerebroventricular (i.c.v.) administrat
ion of 5,7-DHT reduced 5-HT content in the forebrain to 50.5% and that in t
he spinal cord to 10.5%, while intrathecal (i.t.) administration of 5,7-DHT
decreased 5-HT content in the spinal cord to 8.9% without causing any chan
ge in the forebrain. In contrast, noradrenaline or dopamine content was nut
affected by the neurotoxin in both tissues. These treatments significantly
attenuated the muscle tone in the animal models. Moreover, the measurement
of 5-HT and 5-hydroxyindoleacetic acid content in intact rats after decere
bration showed that facilitation of the 5-HT turnover in the spinal cord, b
ut nor in the forebrain, was enhanced compared with sham-operated rats. The
se findings suggest that the descending serotonergic pathways are essential
to induce excessive muscle tone in the intercollicular decerebrated rats a
nd that 5-HT antagonists might be candidates for centrally acting muscle re
laxants. (C) 2000 Elsevier Science B.V. All rights reserved.