Incubation of Negative Affect during Protracted Alcohol Withdrawal Is Age-, but Not Sex-Selective

Abstract

A prior history of excessive drinking induces a negative affective state in both humans and laboratory rodents, the manifestation of which varies with the age of drinking-onset. In adolescent male mice, negative affect incubates over the course of a 30-day alcohol withdrawal period. In contrast, the negative affect exhibited by adult male mice is robust at 1 day withdrawal, but dissipates with the passage of time. As females tend to consume more alcohol than males, we aimed to explore the affective disturbances exhibited by adolescent and adult C57BL/6J mice of both sexes during more protracted alcohol withdrawal and to relate any behavioral changes observed to plasma corticosterone levels as a biochemical index of stress. Male and female, adolescent and adult, mice were subjected to 14 consecutive days of binge alcohol-drinking using a multi-bottle-choice Drinking-in-the-Dark (DID) procedure (5, 10, 20 and 40% v/v). Age- and sex-matched control mice consumed water only. On either withdrawal day 1 or 70, subgroups of animals were subjected a to 1-day behavioral test battery that included the light–dark box shuttle test, marble-burying test, and Porsolt forced swim test. As expected, adolescent mice consumed more alcohol than adults and females consumed more alcohol than males. However, despite binge-like levels of alcohol consumption, we detected relatively few signs of alcohol withdrawal-induced negative affect and there was no correlation between affective behavior and circulating corticosterone levels. We discuss these findings within the context of our published work, highlighting procedural differences that might account for the relatively weak effect of binge-drinking history upon anxiety and depressive-like behavior observed herein.

Alcohol-Drinking Under Limited-Access Procedures During Mature Adulthood Accelerates the Onset of Cognitive Impairment in Mice

“…As a result of other ongoing drinking studies, there was insufficient space in the holding room to individually house water control mice (Water) from Experiment 1 and the large size of the Experiment 3 study precluded singly-housing the Water mice involved in this study. Thus, the Water mice in Experiments 1 and 3 were handled daily by being placed, with their cage mates, into a novel drinking cage on the same free-standing rack as the DID mice and were presented with a single sipper tube containing water, as conducted in prior work (e.g., Lee et al, 2018b ; Szumlinski et al, 2019 ; Jimenez Chavez et al, 2020 ). In Experiment 2, both the DID and Water animals were housed in individual drinking cages during the 3 h period, with the Water mice presented with one sipper tube filled with water during the 2 h drinking session (e.g., Cozzoli et al, 2012 ; Lee et al, 2016 ).…”

“…Samples were stored at −20°C until processing. As conducted in recent reports (e.g., Fultz and Szumlinski, 2018 ; Jimenez Chavez et al, 2020 , 2021 ), headspace gas chromatography was employed to analyze blood ethanol concentrations (BECs) and, with the exception of the male isogenic B6J mice, BECs were determined within 7–10 days of sample collection. BECs were determined using a Shimadzu GC-2014 gas chromatography system (Shimadzu, Columbia, MD), and the data was determined via the GC Solutions 2.10.00 software.…”

“…First, this strain exhibits a high alcohol-preferring and consuming phenotype (e.g., McClearn and Rodgers, 1959 ; Belknap et al, 1993 ; Wahlsten et al, 2006 ). Second, both adolescent and adult C57BL/6J mice reliably binge-drink alcohol over the course of 1 month under different limited-access procedures (Cozzoli et al, 2009 ; Lee et al, 2015 ), with female mice binge drinking larger amounts of alcohol than males (e.g., Finn et al, 2005 ; Rhodes et al, 2005 ; Szumlinski et al, 2019 ; Jimenez Chavez et al, 2020 ). Third, a sex difference is reported in age-related cognitive decline in alcohol-naïve B6J mice (Benice et al, 2006 ), as well as the related C57BL/6NIA strain (Frick et al, 2000 ).…”

“…A history of binge drinking elicits a negative affective state during early alcohol withdrawal in both male and female young adult mice (i.e., mice aged 2–3 months; Lee et al, 2015 ; Szumlinski et al, 2019 ; Jimenez Chavez et al, 2020 ); however, the affective consequences of binge drinking have not been explored in older animals. To address the potential contribution of withdrawal-induced anxiety to the severe impairment in visually-cued navigation exhibited by the binge drinking mice of both Experiments 1 and 2, all mice in Experiment 3 were first screened for a negative affective state, the day prior to commencing cognitive testing procedures.…”

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

“…In some of these studies direct comparisons among strains (97,131,132) and/or age of the animals (133,134), which are critically-relevant variables, were performed but no sex-related effect was found. There are however, a few reports showing that females are more (135)(136)(137)(138) or less (139)(140)(141)(142)(143) anxious than males.…”