Social Housing Leads to Increased Ethanol Intake in Male Mice Housed in Environmentally Enriched Cages

Abstract

An individual's social environment affects alcohol intake. However, the complex interactions between social context and alcohol intake remain understudied in preclinical models. In the present study, we sought to characterize the effects of social housing on voluntary ethanol intake in male C567BL/6J mice using a continuous access two-bottle choice model. This was accomplished using HM2 cages, which allow for the continuous monitoring of individuals' fluid intake through radiofrequency tracking while they remain undisturbed in a group setting. These cages are moderately environmentally enriched compared to standard shoebox cages. By analyzing the levels of voluntary ethanol intake between socially- and individually-housed mice in HM2 cages, we were able to parse apart the effects of environmental enrichment vs. social enrichment. We found that while intake levels were overall lower than those observed when animals are singly housed in standard shoebox cages, socially-housed males consumed significantly more ethanol compared to individually-housed mice, suggesting that while environmental enrichment attenuates ethanol intake, social enrichment may, in fact, potentiate it. This effect was not specific for alcohol, however, in that ethanol preference did not differ as a product of social context. We also found that the total number of non-consummatory channel entries were consistently higher in individually-housed mice. Additionally, a single corticotropin releasing factor receptor 1 antagonist treatment significantly decreased both water and ethanol intake in socially- and individually-housed mice up to 3 h post-treatment, though the effect on water intake was longer lasting. This treatment also significantly decreased the number of non-consummatory channel entries in individually-housed mice, but not in socially-housed mice, suggesting that increased channel visits may be a stress-related behavior. Lastly, we examined blood ethanol concentrations and FosB immunoreactivity to characterize the physiological responses to ethanol intake in socially- and individually-housed mice. The number of FosB-positive cells in the centrally-projecting Edinger-Westphal nucleus and nucleus accumbens shell positively correlated with average baseline ethanol intake in individually-housed mice, but not in socially-housed mice. Overall, we found that social, but not environmental, enrichment can increase ethanol intake in male C57BL/6J mice. Future studies need to test this phenomenon in female mice and assess the generalizability of this finding.

Effects of social housing on alcohol intake in mice depend on the non-social environment

“…This continued for 2 days, after which, 3% ethanol bottles were swapped to 6% ethanol in autoclaved water for the next 3 days ( Figure 1E ). We did not use higher concentrations of ethanol because our previous experiments indicated that mice strongly reduced intake of ethanol in HM2 cages when higher than 6% solutions were used ( Caruso et al, 2021 ; Fulenwider et al, 2021 ). In standard shoebox cages, the position of ethanol and water bottles were swapped daily to avoid side preference bias.…”

“…Although the overall number of licks in lickometer cages correlates with alcohol drinking in many studies ( Ford et al, 2005 ; Griffin et al, 2007 ; Anacker and Ryabinin, 2013 ), lick sizes may differ across various fluids, circadian phases, or experimental conditions. To circumvent this potential problem, we have recently adopted the tracking of consummatory behaviors using radio frequency identification (RFID) tags in Heardsman-2 (HM2) cages ( Thomsen et al, 2017 ; Caruso et al, 2021 ; Fulenwider et al, 2021 ; Walcott and Ryabinin, 2021 ). The HM2 cages are typically large, allowing group housing of rodents.…”

“…Using the HM2 caging system in male C57 mice, we have observed that while single-housed mice display very low alcohol intake in a two-bottle choice (2 BC) procedure, mice housed at four animals per cage had a higher intake of alcohol per mouse ( Caruso et al, 2021 ; Fulenwider et al, 2021 ). This finding suggested that non-social and social differences in housing conditions can produce varied effects on alcohol intake: non-social complexity of HM2 cages contributes to lower alcohol intake, whereas the social complexity of group housing contributes to increased alcohol intake in these cages.…”

Chemogenetic inhibition of corticotropin-releasing factor neurons in the central amygdala alters binge-like ethanol consumption in male mice.

“…During surgical recovery and behavioral studies, mice were individually housed without any environmental enrichment. Single-housing was necessary to get accurate measurements of individual drinking as well as because both social dynamics (Fulenwider et al, 2021) and environmental enrichment can impact ethanol consumption (Holgate et al, 2017). The procedures used in this study were all approved by the University of North Carolina Institutional Animal Care and Use Committee and followed the Guidelines for the Care and Use of Laboratory Animals (National Research Council, 2011).…”

A novel mouse home cage lickometer system reveals sex- and housing-based influences on alcohol drinking

“…The copyright holder for this preprint (which this version posted May 23, 2024. ; https://doi.org/10.1101/2024.05.22.595186 doi: bioRxiv preprint cage (Panksepp et al, 2017). Specialized housing environments, such as the IntelliCage (Holgate et al, 2017) and HM2 cage (Fulenwider et al, 2021), have been valuable tools in studying the efects of social housing and enrichment on consummatory behavior. However, these systems are costly and require specialized housing.…”