Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat s
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ORIGINAL INVESTIGATION
Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat stress Michel Engeln 1 & Megan E. Fox 1 & Mary Kay Lobo 1 Received: 29 May 2020 / Accepted: 31 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Stress exposure has a lasting impact on motivated behavior and can exacerbate existing vulnerabilities for developing a substance use disorder. Several models have been developed to examine how stressful experiences shape drug reward. These range from locomotor sensitization and conditioned place preference to the propensity for drug self-administration or responding to drug-predictive cues. While self-administration studies are considered to have more translational relevance, most of the studies to date have been conducted in rats. Further, many self-administration studies are conducted in single-housed animals, adding the additional stressor of social isolation. Objectives We sought to establish how chronic social defeat stress (CSDS) and social housing conditions impact cocaine selfadministration and cocaine-seeking behaviors in C57BL/6 mice. Methods We assessed self-administration behavior (cocaine or saline, 0.5 mg/kg/infusion) in C57BL/6 mice subjected to 10-day CSDS or in unstressed controls. Mice were housed either in pairs or in isolation during self-administration. We compared the effect of housing on acquisition of self-administration, seeking, extinction, drug-induced reinstatement, and after re-exposure to the social stressor. Results Pair-housing during self-administration revealed increased social avoidance after CSDS is associated with decreased cocaine intake. In contrast, single-housing revealed stress-sensitive cocaine intake, with increased social avoidance after CSDS associated with increased early cocaine intake. Pair-, but not single-housed mice are susceptible to drug-induced reinstatement independent of CSDS history. Stress re-exposure sensitized cocaine-seeking in stressed single-housed mice. Conclusions The social context surrounding cocaine intake can bidirectionally influence cocaine-related behaviors after psychosocial stress and should be considered when studying stress and drug cross-sensitization. Keywords Cocaine . Chronic social defeat stress . Self-administration . Social-isolation . Drug-seeking . Extinction . Reinstatement
Introduction Acute, moderate stress prepares animals to react to challenging stimuli by activating the hypothalamic pituitary Michel Engeln and Megan E. Fox contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05657-y) contains supplementary material, which is available to authorized users. * Mary Kay Lobo [email protected] 1
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St HSFII Building, Rm 265, Baltimore, MD 21201, USA
adrenal (HPA) axis. However, repeated or severe stress has negative and deb
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