PMID- 10727628
OWN - NLM
STAT- MEDLINE
DCOM- 20000615
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 860
IP  - 1-2
DP  - 2000 Mar 31
TI  - Reduction in excessive muscle tone by selective depletion of serotonin in 
      intercollicularly decerebrated rats.
PG  - 104-11
AB  - 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.
FAU - Sakai, M
AU  - Sakai M
AD  - Eisai Tsukuba Research Laboratories, 5-1-3 Tokodai, Tsukuba, Japan. 
      m2-sakai@hhc.eisai.co.jp
FAU - Matsunaga, M
AU  - Matsunaga M
FAU - Kubota, A
AU  - Kubota A
FAU - Yamanishi, Y
AU  - Yamanishi Y
FAU - Nishizawa, Y
AU  - Nishizawa Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Muscle Relaxants, Central)
RN  - 0 (Serotonin Agents)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 5,7-Dihydroxytryptamine/administration & dosage/pharmacology/*therapeutic use
MH  - Animals
MH  - Decerebrate State/*physiopathology
MH  - Dopamine/metabolism
MH  - Efferent Pathways/physiology
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Injections, Intraventricular
MH  - Injections, Spinal
MH  - Male
MH  - Microdialysis
MH  - Muscle Hypertonia/*drug therapy/physiopathology
MH  - Muscle Relaxants, Central/administration & dosage/pharmacology/*therapeutic use
MH  - Muscle Tonus/drug effects
MH  - Norepinephrine/metabolism
MH  - Prosencephalon/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*physiology
MH  - Serotonin Agents/pharmacology/*therapeutic use
MH  - Spinal Cord/*metabolism
EDAT- 2000/03/23 09:00
MHDA- 2000/06/17 09:00
CRDT- 2000/03/23 09:00
PHST- 2000/03/23 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/03/23 09:00 [entrez]
AID - S0006-8993(00)02022-9 [pii]
AID - 10.1016/s0006-8993(00)02022-9 [doi]
PST - ppublish
SO  - Brain Res. 2000 Mar 31;860(1-2):104-11. doi: 10.1016/s0006-8993(00)02022-9.