Assessing effects of oxytocin on alcohol consumption in socially housed prairie voles using radio frequency tracking

Abstract

Alcohol use disorder affects millions of people each year. Currently approved pharmacotherapies have limited success in treating this disorder. Evidence suggests that this lack of success is partly due to how these pharmacotherapies are tested in preclinical settings. The vast majority of preclinical studies assessing the effects of pharmacotherapies on alcohol or drug self‐administration are done in individually housed animals. However, it is known that alcohol and drug intake are heavily influenced by social settings. Here, we adapted radio frequency tracking technology to determine the effects of oxytocin, a potential therapy for alcohol use disorder, on alcohol consumption in socially housed male and female prairie voles. Voluntary alcohol consumption in these animals resulted in high daily alcohol intakes, blood ethanol concentrations that are considered intoxicating, and central changes in FosB immunoreactivity, indicative of changes in neural activity. Prairie voles that received oxytocin temporarily reduced alcohol consumption but not alcohol preference, compared with control prairie voles regardless whether their cagemates received a similar treatment or not. Our results demonstrate that oxytocin can decrease consummatory behaviors in the presence of peers that are not receiving this treatment, and therefore, its potential use in clinical trials is warranted. Moreover, effectiveness of other pharmacotherapies in preclinical studies can be tested in mixed‐treatment socially housed animals similarly to clinical studies in humans.

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

“…Trunk blood was collected for the first cohort of animals 3 h into the dark cycle (27 h following drug injection) and BECs were analyzed using an Analox Analyzer (Analox Instruments, Luneburg, MO, USA) as previously described (Walcott and Ryabinin, 2020).…”

“…Brains were sliced coronally at 30 µM using a Leica cryostat. Sections were then stained for FosB as previously described (Walcott and Ryabinin, 2020). Briefly, sections were incubated with primary antibody targeting FosB protein (rabbit anti-FosB, 1:27000, Lot GR214900-1, Abcam) followed by incubation in biotinylated goat anti-rabbit secondary (1:200, Vector Laboratories).…”

“…The system was initially developed to track food consumption in preclinical obesity research by matching animal's proximity to the food trough with measurement of weight changes of the provided food using a precision balance (Axel et al, 2010;Thomsen et al, 2017). The system was then modified to measure fluid consumption and adapted to study ethanol consumption (Thomsen et al, 2017;Walcott and Ryabinin, 2020). The system consists of a large communal cage with two protruding channels.…”

Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE

“…Despite previous demonstrations of OXT's efficacy in decreasing measures associated with AUD preclinically [27][28][29][30][31][32] and clinically [33][34][35], the molecular mechanisms of OXT's effects remain elusive including its transport into the brain. OXT is thought to cross the blood-brain barrier (BBB) [36].…”

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

“…Indeed, OXT administration decreased alcohol self-administration in numerous preclinical studies ( 16 , 18 – 21 ). Importantly, OXT was effective in translationally relevant animal models, including being administered via intranasal (IN) routes, in models of severe alcohol dependence ( 22 ), in prairie voles, which share similarities in neurocircuitry regulating social behaviors ( 21 ), and in presence of untreated peers, similarly to medication administration in outpatient clinics ( 23 , 24 ). Initial clinical studies also indicated that OXT administration in humans could decrease signs of withdrawal and craving and inhibit excessive alcohol drinking ( 12 , 17 , 25 ).…”