title: Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats.
abstract: Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered "addiction-prone," whereas bLR rats are "addiction-resilient," at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to "sign-track."
  
  
  
  We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e., sign- vs. goal-tracking) and hippocampal neurogenesis.
  
  
  
  bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33-39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62-75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed toward the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry.
  
  
  
  Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats.
  
  
  
  Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.
authors.affiliation: IUNICS/IdISPa, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07122, Palma de Mallorca, Spain. j.garcia@uib.es.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: García-Fuster
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Aram
authors.initials: A
authors.lastname: Parsegian
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.|Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.|Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.|Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Shelly B
authors.initials: SB
authors.lastname: Flagel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D006040:Goals; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: D003042:Cocaine
keywords: Adolescence; Cocaine; Hippocampus; Neurogenesis; Pavlovian conditioning