Tracking natural substance use with home-cage monitoring

Tracking natural substance use with home-cage monitoring

How well do your animal experiments reflect what’s going on in real-world situations in humans? Translatability is one of the biggest challenges of animal research, and never more so than in research areas that investigate complex interactions between biology, psychology and sociology.

One example is substance use and addiction. Whether people do or don’t get hooked on substances like alcohol, cocaine, nicotine depends on both genetics and environment. Time of day, social context, life events: these are just some of the variables that can affect substance abuse. But how do you model these factors in animal research, especially behavioural experiments that are only done at certain times of the day?

 

Home-cage substance use

A recent study from Wong et al., 2022 showcased a home cage monitoring system that tracks social interactions and self-administered substance use 24/7 in mice. The home-cage system was developed especially for Wong et al., at University Washington, USA. The system is open access, with low-cost hardware and software for controlling behavioural experiments.

The system housed 24 mice and was complete with sleeping chambers interconnected with feeding and drinking stations via plastic tubes. Animal behaviours like social interaction and substance use habits were continuously monitored using RFID (radiofrequency identification) transponder systems and overhead video cameras.

The proof-of-concept study investigated preferences and intake of flavours of Kool-Aid, a sugary and addictive drink. Special drinking stations were equipped with an RFID sensor and each animal was implanted with an RFID transponder, so how much each animal drinks, and when, is tracked via the sensors. Social interaction behaviours were also monitored using overhead video cameras.

 

Mouse drinking habits depend on circadian rhythms

What did they find? First of all, mice drink more Kool-Aid at night, but tend to do shorter, more frequent visits at night than during the day. Female mice were more hooked on Kool-Aid, as they visited the drinking stations more frequently than males. And there were differences in taste too: males preferred either grape or orange, females orange or cherry.

According to the authors, the findings highlight the ability of the cages to examine polysubstance over long time periods, revealing significant sex and individual differences in substance use. Their future work aims to investigate preferences of alcohol and a range of different psychoactive drugs like fentanyl, cocaine, and benzodiazepines.

 

Data accuracy and reproducibility

While the study was more proof-of-concept, its aim was to demonstrate the ability of the system to continuously monitor the behaviour of individual rodents in group environments. But what benefits does the system have, and how can it be used in other areas of research?

For one, the home-cage system records behaviours in rodent’s natural sleep/wake cycles without the influence of human experimenters. This allows experimenters to study circadian rhythm cycles and animal’s natural behaviours with more accuracy and with less human bias. Studies have shown that home-cage monitoring helps to enhance experimental reproducibility.

Automatic behaviour tracking is a huge boon for neuroscience. The home-cage system presented by Wong et al., automatically collected huge amounts of data about the natural drinking habits of animals. The decision of what data the experimenters will extract of course depends on the experimental design and research question, but the system nevertheless allows access to rich behavioural repertoires of animals. And with the help of open source software like DeepLabCut to integrate RFID and video data, users can perform high-throughput analysis in large cohorts of animals.

 

The full potential of home-cage monitoring systems is yet to be seen. Much of this depends on the power of the systems to collect rich, biologically meaningful data, but in a way that is accessible to analyse. Cost is also a factor; many see a technological gap in affordable animal tracking systems.

Similar systems are being used in many fields of neuroscience to track natural animal behaviours, including cognitive function, learning, and a variety of social behaviours like individuality. What is different about the system used by Wong et al.,? It mostly comes down to accessibility.

In the study, Wong et al., described the cage system as:

“…a first step towards designing a rodent model of substance use that close resembles the experience of people who use drugs.”