Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats

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ORIGINAL INVESTIGATION

Role of adolescent-formed, context-drug-associations on reinstatement of drug-seeking behavior in rats Bo Ram Cho 1 & Jennifer Gerena 1 & Doris I. Olekanma 1 & Aneesh Bal 1 & André N. Herrera Charpentier 1 & Amy A. Arguello 1 Received: 11 October 2019 / Accepted: 1 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Rationale Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared with adults; however, the contribution of adolescent-formed, context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced, cocaine-seeking during adolescence vs adulthood are unknown. Objectives The present study compared the effect of adolescent vs adult-formed context-drug associations under different housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified abbreviated (ABRV) paradigm. Methods In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2 h, 1×/day, 10 days), and extinction training (EXT) in a second context (1 h, 1×/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2 and 3, rats received all behavioral phases during adolescence or adulthood: ABRV CocSA (2 h, 2×/day, 5 days), EXT (1 h, 4×/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions. Results and conclusions Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under NonABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced, cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence. Keywords Adolescence . Context . Self-administration . Cocaine seeking . Reinstatement . Isolation housing . Pair housing . Extinction

Introduction Adolescence is a developmental time period characterized by increased sensation seeking, impulsivity, and initiation of drug use (Spear and Silveri 2016; Steinberg 2016; Walker et al. Bo Ram and Jennifer are co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05575-z) contains supplementary material, which is available to authorized users. * Amy A. Arguello [email protected] 1

Psychology Department, Michigan State University, Interdisciplinary Science and Technology Building, West Lab Rm 4100, 766 Service Rd, East Lansing, MI 48824, USA

2017; Dahl et al. 2018). Adolescent initiation o