Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice.

Hyperkateifia and stress-induced alcohol cravings drive relapse in individuals with alcohol use disorder (AUD). The brain stress signal norepinephrine (also known as noradrenaline) tightly controls cognitive and affective behavior and was thought to be broadly dysregulated with AUD. The locus coeruleus (LC) is a major source of forebrain norepinephrine, and it was recently discovered that the LC sends distinct projections to addiction-associated regions suggesting that alcohol-induced noradrenergic changes may be more brain region-specific than originally thought. Here we investigated whether ethanol dependence alters adrenergic receptor gene expression in the medial prefrontal cortex (mPFC) and central amgydala (CeA), as these regions mediate the cognitive impairment and negative affective state of ethanol withdrawal. We exposed male C57BL/6J mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and assessed reference memory, anxiety-like behavior and adrenergic receptor transcript levels during 3-6 days of withdrawal. Dependence bidirectionally altered mouse brain α1 and ß receptor mRNA levels, potentially leading to reduced mPFC adrenergic signaling and enhanced noradrenergic influence over the CeA. These brain region-specific gene expression changes were accompanied by long-term retention deficits and a shift in search strategy in a modified Barnes maze task, as well as greater spontaneous digging behavior and hyponeophagia. Current clinical studies are evaluating adrenergic compounds as a treatment for AUD-associated hyperkatefia, and our findings can contribute to the refinement of these therapies by increasing understanding of the specific neural systems and symptoms that may be targeted.

Aspen shaving versus chip bedding: effects on breeding and behavior.

The choice of laboratory cage bedding material is often based on both practical and husbandry issues, whereas behavioral outcomes rarely appear to be considered. It has been noted that a breeding success difference appears to be associated with the differential use of aspen chip and aspen shaving bedding in our facility; therefore, we sought to analyze breeding records maintained over a 20-month period. In fact, in all four mouse strains analyzed, shaving bedding was associated with a significant increase in average weanlings per litter relative to chip bedding. To determine whether these bedding types also resulted in differences in behaviors associated with wellbeing, we examined nest building, anxiety-like, depressive-like (or helpless-like), and social behavior in mice housed on chip versus shaving bedding. We found differences in the nests built, but no overall effect of bedding type on the other behaviors examined. Therefore, we argue that breeding success, perhaps especially in more challenging strains, is improved on shaving bedding and this is likely due to improved nest-building potential. For standard laboratory practices, however, these bedding types appear equivalent.