Reduction in excessive muscle tone by selective depletion of serotonin in intercollicularly decerebrated rats.
Intercollicular decerebration in animals induces sustained facilitation of muscle tone of the limbs and this animal model has been used to assess centrally 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 important role in locomotion. Alteration of muscle tone has been investigated in 5-HT-depleted rats with a neurotoxin, 5, 7-dihydroxytryptamine (5,7-DHT) after pretreatment with desipramine. Intracerebroventricular (i.c.v.) administration of 5,7-DHT reduced 5-HT content in the forebrain to 50.5% and that in the 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 change in the forebrain. In contrast, noradrenaline or dopamine content was not 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 decerebration showed that facilitation of the 5-HT turnover in the spinal cord, but not in the forebrain, was enhanced compared with sham-operated rats. These findings suggest that the descending serotonergic pathways are essential to induce excessive muscle tone in the intercollicular decerebrated rats and that 5-HT antagonists might be candidates for centrally acting muscle relaxants.
Sakai
M
M
Eisai Tsukuba Research Laboratories, 5-1-3 Tokodai, Tsukuba, Japan. m2-sakai@hhc.eisai.co.jp
Matsunaga
M
M
Kubota
A
A
Yamanishi
Y
Y
Nishizawa
Y
Y
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003655:Decerebrate State / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D004525:Efferent Pathways / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis; D009122:Muscle Hypertonia / Q000188:drug therapy* / Q000503:physiopathology; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009129:Muscle Tonus / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013116:Spinal Cord / Q000378:metabolism*
D009125:Muscle Relaxants, Central; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D009638:Norepinephrine