A novel mouse model for vulnerability to alcohol dependence induced by early-life adversity

Agbonlahor Okhuarobo, Jessica L. Bolton, Ighodaro Igbe,

Eric P. Zorrilla, Tallie Z. Baram, and Candice Contet

Neurobiol Stress. 2020 Nov; 13: 100269. 

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  • Childhood adversity increases vulnerability to alcohol use disorders and preclinical models are needed to investigate the underlying neurobiological mechanisms.

  • The present study modeled early-life adversity by rearing male and female C57BL/6J mouse pups in a limited bedding and nesting (LBN) environment, which induces erratic maternal care.

  • We tested the hypothesis that LBN rearing might exacerbate or facilitate the emergence of the motivational and affective effects of chronic intermittent ethanol (CIE).

  • LBN-reared males escalated their ethanol intake at an earlier stage of CIE exposure

  • LBN-reared CIE-exposed males showed reduced open arm exploration in the elevated plus maze and increased immobility in the tail suspension test compared to alcohol-naïve counterparts

  • In summary, the LBN experience accelerates the transition from moderate to excessive alcohol drinking and produces additional indices of affective dysfunction during alcohol withdrawal in C57BL/6J male mice.

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Note: this figure includes highlights from original figures 1, 2, and 4.  A. Experimental timeline. C57BL/6J male and female pups were reared under limited bedding and nesting (LBN) or control conditions from postnatal days (P) 2–9. Once mice reached adulthood, they were subjected to limited-access two-bottle choice (2BC) ethanol drinking (grey boxes). Once ethanol intake stabilized, some of the mice were exposed to chronic intermittent ethanol (CIE) vapor inhalation (blue boxes). 2BC sessions were alternated with vapor inhalation over the course of 14–16 weeks. After their last week of 2BC, males were subjected to the elevated plus maze (EPM), digging (Dig), splash (Groom), and tail suspension (TST) tests. They were then exposed to an additional week of CIE and tested in the tail pressure test (TPT) 32 h into withdrawal. After a final week of CIE, they were tested for novel object recognition (NOR) and blood was collected for corticosterone measurement (Cort). B. Weekly ethanol intake during CIE exposure. *, t-test, Air-2BC vs. CIE-2BC, p < 0.05. C. Elevated plus maze: % time spent on the open arms. *, t-test, LBN Air-water vs LBN CIE-2BC, p < 0.05. D. Tail suspension test: immobility duration. ***, t-test, LBN Air-water vs LBN CIE-2BC, p < 0.001.