Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat stress
Psychopharmacology. 2020-09-10; 238(1): 41-54
DOI: 10.1007/s00213-020-05657-y
Lire sur PubMed
Engeln M(#)(1), Fox ME(#)(1), Lobo MK(2).
Author information:
(1)Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St HSFII Building, Rm 265, Baltimore, MD, 21201, USA.
(2)Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St HSFII Building, Rm 265, Baltimore, MD, 21201, USA. .
(#)Contributed equally
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 self-administration 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.