title: Prolonged striatal disinhibition as a chronic animal model of tic disorders.
abstract: BACKGROUND
  Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABAAantagonists into the striatum, leading to temporary disinhibition.
  
  
  METHODS
  The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum.
  
  
  RESULTS
  Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period.
  
  
  METHODS
  The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression.
  
  
  CONCLUSIONS
  The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder.
authors.affiliation: Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Vinner
authors.affiliation: Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Israelashvili
authors.affiliation: Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel. Electronic address: izhar.bar-gad@biu.ac.il.
authors.forename: Izhar
authors.initials: I
authors.lastname: Bar-Gad
mesh_terms: D000200:Action Potentials; D000818:Animals; D001640:Bicuculline; D002408:Catheters, Indwelling; D002908:Chronic Disease; D003342:Corpus Striatum / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D015918:Infusion Pumps, Implantable; D009474:Neurons / Q000502:physiology; D020318:Rats, Long-Evans; D013981:Tic Disorders / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001640:Bicuculline
keywords: Basal ganglia; Motor tics; Osmotic pump; Striatum; Tourette syndrome