[Curative effect and possible mechanisms of topiramate in treatment of Tourette syndrome in rats].
OBJECTIVE
The pathogenesis of Tourette syndrome (TS) is associated with the disorders of neurotransmitters, such as dopamine (DA) and excitatory amino acids (EAA). Antiepileptic drugs such as topiramate have shown some effects on TS, but the mechanism has not been clearly identified. The objective of the research was to evaluate the relationship between the pathogenesis of TS and abnormality of neurotransmitters by determining the levels of brain free DA and plasma EAA in iminodipropionitrile (IDPN) induced head twitch response (HTR) rats, and to investigate the effects of topiramate on HTR induced by IDPN.


METHODS
Forty-eight Sprague-Dawley rats were randomly divided into six groups: blank control, TS model, and haloperidol-(0.5 mg/kg) and topiramate-treated (5, 10 and 20 mg/kg). HTR was induced by 7-day peritoneal injections of IDPN (150 mg/kg daily) and was used as TS model. Brain free DA levels and plasma levels of EAA were measured using ELISA and high performance liquid chromatography respectively 35 days after haloperidol or topiramate administration.


RESULTS
Brain free DA levels were significantly lower and plasma EAA levels were significantly higher in the TS model group compared with those in the blank control group (P<0.05). Topiramate of 10 and 20 mg/kg significantly decreased the frequency of IDPN-induced HTR and significantly increased the level of brain free DA when compared with the TS model group (P<0.05). Topiramate of 20 mg/kg treatment as haloperidol treatment significantly decreased plasma EAA levels compared with the TS model group (P<0.05).


CONCLUSIONS
The pathogenesis of TS is related to the super-sensitivity of DA receptor in the center nervous system and the over-effect of plasma EAA. Topiramate can reduce IDPN-induced HTR, probably through the inhibition of DA and DA-receptor combination in the brain and the secretion and release of plasma EEA.
Guo
Hui
H
Department of Pediatrics, People's Hospital of Sichuan Province, West China School of Clinical Medicine, Chengdu 610072, China.
Ou-Yang
Ying
Y
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D018846:Excitatory Amino Acids / Q000097:blood; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077236:Topiramate; D005879:Tourette Syndrome / Q000188:drug therapy*
D000927:Anticonvulsants; D018846:Excitatory Amino Acids; D000077236:Topiramate; D005632:Fructose; D004298:Dopamine