title: Cocaine-seeking behavior in a genetic model of attention-deficit/hyperactivity disorder following adolescent methylphenidate or atomoxetine treatments.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with cocaine abuse. Controversy exists regarding long-term consequences of ADHD medications on cocaine abuse liability. Whereas childhood methylphenidate treatment may be preventative, methylphenidate in teens appears to further increase later cocaine abuse risk. In rodents, adolescent methylphenidate treatment further increases adult cocaine self-administration in the Spontaneously Hypertensive Rat (SHR) model of ADHD, whereas adolescent atomoxetine treatment does not. Effects of ADHD medications on cocaine cue reactivity, a critical component of addiction, are unknown.
  
  
  METHODS
  To investigate this, SHR, Wistar-Kyoto (inbred control) and Wistar (outbred control) rats received therapeutically relevant doses of methylphenidate (1.5 mg/kg, oral) and atomoxetine (0.3 mg/kg, intraperitoneal), or respective vehicles from post-natal day 28-55. Cocaine seeking, reflecting cue reactivity, was measured in adulthood during self-administration maintenance and cue-induced reinstatement tests conducted under a second-order schedule.
  
  
  RESULTS
  Compared to control strains, SHR earned more cocaine infusions, emitted more cocaine-seeking responses during maintenance and reinstatement testing, and required more sessions to reach the extinction criterion. Compared to vehicle, adolescent methylphenidate, but not atomoxetine, further increased cocaine intake during maintenance testing in SHR. Adolescent atomoxetine, but not methylphenidate, decreased cocaine seeking during reinstatement testing in SHR. Neither medication had effects on cocaine intake or cue reactivity in control strains.
  
  
  CONCLUSIONS
  The SHR successfully model ADHD and cocaine abuse comorbidity and show differential effects of adolescent ADHD medications on cocaine intake and cue reactivity during adulthood. Thus, SHR have heuristic value for assessing neurobiology underlying the ADHD phenotype and for evaluating pharmacotherapeutics for ADHD.
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.
authors.forename: Chloe J
authors.initials: CJ
authors.lastname: Jordan
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.
authors.forename: Roxann C
authors.initials: RC
authors.lastname: Harvey
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.
authors.forename: Britahny B
authors.initials: BB
authors.lastname: Baskin
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA. Electronic address: kkantak@bu.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kantak
mesh_terms: D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D011437:Propylamines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride
keywords: Addiction; Atomoxetine; Attention-deficit/hyperactivity disorder; Cocaine; Methylphenidate; Spontaneously Hypertensive Rat