M Julia García-Fuster1, Aram Parsegian2, Stanley J Watson2,3, Huda Akil2,3, Shelly B Flagel2,3. 1. IUNICS/IdISPa, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07122, Palma de Mallorca, Spain. j.garcia@uib.es. 2. Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. 3. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Abstract
RATIONALE: 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." OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.
RATIONALE: 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." OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.
Authors: Chelsea R McCoy; Mohammad N Sabbagh; Jonathan P Huaman; Alicia M Pickrell; Sarah M Clinton Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2019-07-19 Impact factor: 5.067
Authors: Brittany N Kuhn; Paolo Campus; Marin S Klumpner; Stephen E Chang; Amanda G Iglesias; Shelly B Flagel Journal: Psychopharmacology (Berl) Date: 2021-06-28 Impact factor: 4.530