Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

作者：Julia Garcia Fuster M; Parsegian Aram; Watson Stanley J; Akil Huda; Flagel Shelly B

来源：Psychopharmacology, 2017, 234(8): 1293-1305.

DOI：10.1007/s00213-017-4566-0

• Adolescence
• Cocaine
• Pavlovian conditioning
• Hippocampus
• Neurogenesis

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 highresponder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-termimpact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are consideredBaddiction-prone," whereas bLR rats are Baddictionresilient," at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to Bsign-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.
Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.

• 出版日期2017-4