title: Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats.
abstract: BACKGROUND
  Methylphenidate is a psychostimulant given for extended periods of time as a treatment of attention-deficit/hyperactivity disorder (ADHD). The long-term effects of the drug are not yet known, and it is speculated that repeated exposure may produce drug dependence.
  
  
  OBJECTIVE
  To investigate the effects of repeated methylphenidate treatment on methylphenidate self-administration and reinstatement in the most validated animal model of ADHD, the spontaneously hypertensive rat (SHR), and Wistar rat, strain representing the "normal" heterogeneous population.
  
  
  METHODS
  Rats were administered intraperitoneally with saline or methylphenidate (2 mg/kg) for 14 days, prior to experiments. Thereafter, responses for intravenous methylphenidate under the fixed ratio (FR1 and FR3) and progressive ratio (PR) schedules were assessed. Extinction experiments followed, as well as tests to determine the ability of intraperitoneal administration of methylphenidate (2 and 5 mg/kg) to reinstate extinguished drug-seeking behaviors in rats.
  
  
  RESULTS
  Previous exposure to methylphenidate enhanced methylphenidate self-administration in Wistar rats but not in SHR (FR3). Methylphenidate pretreatment reduced responding for methylphenidate in SHR but did not affect self-administration behaviors of Wistar rats (PR). Methylphenidate pre-exposure robustly reinstated drug-seeking behaviors in Wistar rats, but not in SHR.
  
  
  CONCLUSIONS
  The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients.
authors.affiliation: Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongreung-dong, Nowon-gu, Seoul, Korea.
authors.forename: Ike
authors.initials: I
authors.lastname: dela Peña
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Jong Chan
authors.initials: JC
authors.lastname: Lee
authors.forename: June Bryan
authors.initials: JB
authors.lastname: dela Peña
authors.forename: Aee Ree
authors.initials: AR
authors.lastname: Sohn
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D013045:Species Specificity
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
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