Rats

Originally domesticated from the wild brown, or Norwegian rat (Rattus norvegicus), laboratory rats are one of the most extensively used rodents in research and were used for over 160,000 (4.6%) licenced research procedures in 2018 (Home Office 2019). While typically docile, laboratory rats retain many of the behaviours of their wild ancestors and will readily present them if given the opportunity (Berdoy 2002).


The Laboratory Rat: A Natural History (Berdoy 2002) follows the lives of domestic rats after being released in a large outdoor enclosure. After only a few hours, the newly released rats began to use a hopping gait characteristic of their wild cousins and to dig burrows, something they had not been able to do in the laboratory for many generations (see 6:30 in video above). Learn more about the film by visiting ratlife.org.

Behaviour

In the wild, rats are social animals living in extended family groups. Norwegian rats excavate and inhabit an extensive network of tunnels and laboratory rats exhibit analogous burrowing behaviour when provided with suitable substrate (Boice 1977; Calhoun 1963; Makowska and Weary 2016). In the wild such burrows would be occupied by a single dominant male, several females and juvenile animals. In the laboratory male rats can be group housed without aggression provided they are placed together before puberty with the most harmonious male groups typically made up of litter mates (Hurst et al. 1999). Prior to giving birth, female rats will isolate themselves from the rest of the group and build a nest. When nursing their young, female rats can behave aggressively towards other animals and handlers and should be isolated in a nursing cage prior to parturition (Pritchett-Corning 2015).

Rats are nocturnal animals and are especially active during the early evening and just before sunrise. They engage in play behaviour (e.g. wrestling and chasing) from a young age and these activities are important for establishing social ties, which adult rats will reinforce by grooming. These behaviours are key to maintaining harmonious groups and should not be misconstrued as aggression (Komorowska and Pellis 2004). Rats also spend periods of time grooming themselves (auto-grooming), an activity that normally forms part of a routine (e.g. following awakening or eating). Rats will also groom themselves as a displacement activity when anxious or threatened, thus protracted or erratic bouts of auto-grooming may be a sign of stress or ill health in an animal and should be investigated (Komorowska and Pellis 2004).

Rats primarily interact with their environment through scent and touch. Pheromones released from scent glands and present in their urine and faeces are used to communicate information such as health, kinship, readiness to breed as well as states of anxiety or distress (Inagaki et al. 2014). When cleaning rat enclosures, care should be taken not to disseminate unfamiliar or conspecific odours as they risk provoking anxiety or aggression. Particular caution should be given when cleaning enclosures with rats during late pregnancy and the first week following birth (Burn 2008; Burn and Mason 2008). Rats also communicate through ultrasonic vocalisations with 22kHz sounds being associated with a state of alarm or distress, while 50kHz sounds reflect a positive emotional state (Panksepp and Burgdorf 2000). Their vision is relatively poor, however they are highly sensitive to motion and will startle in response to rapid or sudden movements (Douglas et al. 2006).

Figure 1. Acclimatised to human interaction, a rat accepts food from its handler's hand.

Rats are omnivorous and if handled and housed appropriately they will readily eat most palatable foods offered to them (Figure 1). Stressed or anxious laboratory rats are cautious when exposed to unfamiliar foods making tentative approaches toward and taking small samples from the item until they regard it as safe (Modlinska, Stryjek and Pisula 2015).
 

Housing

Enclosures

Figure 2. Rats housed in a conventional (18 cm high) cage.

Minimum enclosure sizes for rats in European research establishments are fully detailed in Table 1.2 of Annex III to Directive 2010/63/EU. The minimum permitted floor area for group housed adult rats weighing under 600g is 800cm2 increasing to 1,500cm2 for animals over 600g. The minimum permitted height for a rat enclosure is 18cm (Figure 2). Nevertheless, conventional cages might lead to stiffness and positional stress, as they don’t provide enough space for the rats to perform natural behaviours such as stretching and standing upright. Often rats will resolve to lateral stretching in order to alleviate the negative effect conventional cages have on their posture. Therefore, taller enclosures (26-30cm) are strongly recommended to allow the rats to perform their full natural range of movements (Makowska and Weary 2016).

Figure 3. Rats housed in a Double Decker (38 cm high) cage.

Increasingly laboratories are adopting a new type of rat cage, known as the Double Decker, where the total height of the cage is 38cm, providing more space for the rats to perform natural behaviours (Figure 3). The suitability of these Double Decker cages has also been successfully tested in telemetry studies that have historically been performed on animals housed in single-storey enclosures, opening up new opportunities to increase animal welfare during drug safety screening studies.

Rats show a strong preference for enclosures with solid floors, and exhibit signs of stress and discomfort when housed in cages with wire floors without enrichment (van de Weerd, van den Broekb and Baumansaet 1996). This indicates that they should always be housed in solid floored enclosures unless there is a strong scientific justification not to do so.

While typically less aggressive than mice, risk of aggression between rats can be minimised by establishing groups of animals before they reach puberty and providing additional space or isolation for mothers and their litters. Cage cleaning can have a disruptive effect on groups of rats, not solely because it routinely takes place in the daytime when the animals usually sleep, but also due to placing them in a new environment which will result in an altered pheromonal communication (Abou-Ismail, Darwish and Ramadan 2014; Bind, Minney and Rosenfeld 2013). Rat behaviour is affected for roughly an hour post-cleaning, with reports of aggression and even cannibalism in the case of rats close to partition or with new-born pups (Burn and Mason 2008). Care must be taken to balance the cleaning protocol of rat enclosures with their need to maintain a consistent, controlled environment.

Lighting

Rats are typically housed in artificially lit rooms with a 12-hour light/dark cycle. As a nocturnal species, extended exposure to bright light could have damaging effects to the rat retina, especially albino strains. For that reason, it is recommended that light levels within the enclosure do not exceed 50 lux and racks should ideally have shaded tops to reduce the risk of retinal degeneration (Perez and Perentes 1994).

Temperature

UK guidelines recommend that group-housed rats should be kept at a temperature range between 20°C to 24oC (Home Office 2014). Cages should be provided with a suitable nesting material to allow rats to regulate their microclimate, in addition to allowing them to perform their natural nesting behaviours.

Summary of the key features of rat housing

Rat enclosures must:

1. Be large enough to provide enough space for exercise and normal social behaviour.

2. Be designed with a minimum height of 18 cm, and preferably 26-30cm or more.

3. Be well ventilated.

4. Have solid floors covered with an adequate depth of appropriate substrate (such as dust free Aspen wood chip, Megazorb or Alpha-Dri) for hygiene, comfort and to permit natural foraging and digging behaviour.

5. Contain sheltered areas for resting, security, and managing social interactions.

6. Be softly lit and subject to a light dark cycle.

7. Kept at a temperature range of 20-24oC.

Environmental enrichment

Rats’ enclosures should be structured and maintained to accommodate their core needs and behaviours in the wild (i.e. social contact, hiding, exploration, climbing, foraging, gnawing, and resting). They should be provided with substrate for bedding and insulation at a depth that allows them to engage in digging and foraging behaviour. Studies have shown that size and manipulability are important determinants of bedding preference for rats, with the animals preferring wood-based bedding with a larger particle size such as dust free Aspen wood chip or Megazorb (Blom et al. 1996). Female rats close to partition will seek out and build nests and should be provided with a suitable nesting material such as paper strips (Manser et al. 1998). Naïve male and female rats will also spontaneously build nests if appropriate nesting material is offered to them (Jegstrup et al. 2005). Use of nesting material in rat cages has been shown to have a positive effect on both rat physiology and psychology and should be considered as an enrichment in any rat enclosure (Vitalo et al. 2012).

Dependent on the suitability of the resources, rats prefer a source of shelter above other enrichments such as nesting material, though given the option they will choose to have both (Manser et al. 1998). As such, a shelter hut or box should be included in every cage. Rats prefer shelters with one entrance rather than open-ended tunnels, and long strips of nesting material rather than short ones (Patterson-Kane, Harper and Hunt 2001). If the nest box provided is not suitable, they will only use nesting material, and vice versa (Bradshaw and Poling 1991). If space allows, a hammock should also be included in the cage, though it should not substitute for a nest box unless it is fully enclosed, allowing rats to shelter from the light when sleeping. 

Like many rodents, rats’ front teeth continue to grow throughout their lifetime. Provision of hard items to gnaw on is essential to prevent overgrowth. A hard-pelleted diet should be considered a minimum requirement to maintain tooth length, while inclusion of wood blocks or chew sticks should also be considered. Note that rats may exhibit individual preferences for which item they chew. Additional nutritional enrichment, such as supplementation with different foods or food textures, should be considered if it does not risk influencing the results of study being performed on the animals.

Figure 4. Positive human interactions are a source of dynamic enrichment for rats. Image courtesy of the Preclinical Research Facility, University of Leicester.

Rats are social animals valuing contact with other rats over that of an enlarged or enriched enclosure (Patterson-Kane, Hunt and Harper 2002).  Removing a rat from a stable social group will result in the rest of its cage mates displaying signs of stress (Burman et al. 2008). Rats should not be housed alone without exceptional scientific or animal welfare justification. Where this is necessary, the period of isolation should be kept to a minimum. Apart from rat socialization, positive human interactions are also a source of dynamic enrichment for rats. If acclimatised at a young age, they will quickly become receptive to handling (Figure 4).

Figure 5. Example of a rat being tickled. Image courtesy of Megan LaFollette.

Tickling or playful handling (Figure 5) as opposed to stroking of young rats has been shown to reduce the fearfulness these animals display towards humans when compared to not handling them at all. It can also decrease the aversion rats display to scientific procedures such as intraperitoneal injections (Cloutier et al. 2014; Cloutier et al. 2018). A program of acclimatisation and handling should be considered a standard component of a rat enrichment programme, especially for those animals that will be used for scientific procedures.

Play and exercise areas can also be used to improve rat welfare. Playpens for rats (Figure 6) can be easily created by reusing and repurposing materials in the animal facility (e.g. modified rabbit cages), and enriched with water trays, ladders, ropes, tunnels, substrate and treats scattered throughout. Rats can be given intermittent access to these enriched playpens, from a few minutes to a few hours a day, where they can socialise, exercise and perform natural behaviours that can’t be easily performed in their conventional home cages, such as foraging, climbing, and burrowing. For more information on playpens, see the report of our 2017 IAT Congress workshop.

   

Figure 6. Playpens can provide rats with space to socialize and exercise, resulting in improved welfare. Playpens can be constructed by reusing materials already available in the animal facility (e.g. old rabbit cages). Images courtesy of the Preclinical Research Facility, University of Leicester.



 

Summary of environmental enrichment options for rats

1. Rats should be socially housed and kept either in single sex groups or in stable breeding pairs or trios.

2. Rats require objects to gnaw on (e.g. soft wood blocks, hard pellets, cardboard tubes) to prevent their teeth overgrowing.

3. Rats should be provided with nesting material from a young age (e.g. paper strips, sizzle nest, nestlets) to enable nesting behaviour.

4. You should consider providing rats with access to playpens where they can exercise and socialize.

5. At least one shelter (e.g. cardboard tube or plastic house) should be provided to encourage exploration and provide refuge.

6. A programme of acclimatisation and handling will improve the rat-handler relationship and reduce the stress of scientific procedures.

Related resources

Pritchett-Corning K (2015). Rats. In: Comfortable Quarters for Laboratory Animals (Eds. Liss C, Litwak K, Tilford D, Reinhardt V), Animal Welfare Institute.

Koolas J (2010). The Rat. In: The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals (Ed. Kirkwood RHJ), Wiley-Blackwell.

NC3Rs/AstraZeneca (2017). IAT Congress 2017 workshop summary: Playtime for Rats.

Berdoy M (2002). The Laboratory Rat: A Natural History. Film (27 mins), available at www.ratlife.org.

References

Abou-Ismail UA, Darwish RA, Ramadan GA (2014). Should cages of laboratory rats be enriched physically or socially. Global Veterinaria 13(4): 570-582. doi: 10.5829/idosi.gv.2014.13.04.85237

Berdoy M (2002). The Laboratory Rat: A Natural History. Film (27 mins), available at www.ratlife.org.

Bind RH, Minney SM, Rosenfeld S (2013). The role of pheromonal responses in rodent behavior: future directions for the development of laboratory protocols. Journal of the American Association for Laboratory Animal Science 52(2): 124-129. PMCID: PMC3624779

Blom HJ, Van Tintelen G, van Vorstenbosch CJ et al. (1996). Preferences of mice and rats for types of bedding material. Laboratory Animals 30(3): 234-244. doi: 10.1258/002367796780684890

Boice R (1977). Burrows of wild and albino rats: effects of domestication, outdoor raising, age, experience, and maternal state. Journal of Comparative and Physiological Psychology 91(3): 649-661. doi: 10.1037/h0077338

Bradshaw AL and Poling A (1991). Choice by rats for enriched versus standard home cages: plastic pipes, wood platforms, wood chips, and paper towels as enrichment items. Journal of the Experimental Analysis of Behavior 55(2): 245-250. doi: 10.1901/jeab.1991.55-245

Burman O, Owen D, Abouismail U et al. (2008). Removing individual rats affects indicators of welfare in the remaining group members. Physiology & Behavior 93(1-2): 89-96. doi: 10.1016/j.physbeh.2007.08.001

Burn CC (2008). What is it like to be a rat? Rat sensory perception and its implications for experimental design and rat welfare. Applied Animal Behaviour Science 112(1-2): 1-32. doi: 10.1016/j.applanim.2008.02.007

Burn CC and Mason GJ (2008). Effects of cage-cleaning frequency on laboratory rat reproduction, cannibalism, and welfare. Applied Animal Behaviour Science 114(1-2): 235-247. doi: 10.1016/j.applanim.2008.02.005

Calhoun JB (1963). Ecology and sociology of the Norway rat. Bethesda, U.S. Department of Health, Education, and Welfare, Public Health Service.

Cloutier S, LaFollette MR, Gaskill BN et al. (2018). Tickling, a technique for inducing positive affect when handling rats. Journal of Visualized Experiments 135: 57190. doi: 10.3791/57190

Cloutier S, Wahl K, Baker C et al. (2014). The social buffering effect of playful handling on responses to repeated intraperitoneal injections in laboratory rats. Journal of the American Association for Laboratory Animal Science 53(2): 168-173. PMCID: PMC3966273

Douglas RM, Neve A, Quittenbaum JP et al. (2006). Perception of visual motion coherence by rats and mice. Vision Research 46(18): 2842-2847. doi: 10.1016/j.visres.2006.02.025

Home Office (2014). Mice, rats, gerbils, hamsters and guinea pigs. In: Code of practice for the housing and care of animals bred, supplied or used for scientific purposes, Her Majesty’s Stationery Office.

Home Office (2019). Annual Statistics of Scientific Procedures on Living Animals Great Britain 2018, APS Group.

Hurst JL, Barnard CJ, Tolladay U et al. (1999). Housing and welfare in laboratory rats: effects of cage stocking density and behavioural predictors of welfare. Animal Behaviour 58(3): 563-586. doi: 10.1006/anbe.1999.1165

Inagaki H, Kiyokawa Y, Tamogami S et al. (2014). Identification of a pheromone that increases anxiety in rats. Proceedings of the National Academy of Sciences 111(52): 18751-18756. doi: 10.1073/pnas.1414710112

Jegstrup IM, Vestergaard R, Vach W et al. (2005). Nest-building behaviour in male rats from three inbred strains: BN/HsdCpb, BDIX/OrIIco and LEW/Mol. Animal Welfare 14(2): 149-156.

Komorowska J and Pellis SM (2004). Regulatory mechanisms underlying novelty-induced grooming in the laboratory rat. Behavioural Processes. 67(2): 287-293. doi: 10.1016/j.beproc.2004.05.001

Makowska IJ and Weary DM (2016). The importance of burrowing, climbing and standing upright for laboratory rats. Royal Society Open Science 3(6): 160136. doi: 10.1098/rsos.160136

Manser CE, Broom DM, Overend P et al. (1998). Investigations into the preferences of laboratory rats for nest-boxes and nesting materials. Laboratory Animals 32(1): 23-35. doi: 10.1258/002367798780559365

Modlinska K, Stryjek R, Pisula W (2015). Food neophobia in wild and laboratory rats (multi-strain comparison). Behavioural Processes 113: 41-50. doi: 10.1016/j.beproc.2014.12.005

Panksepp J and Burgdorf J (2000). 50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables. Behavioural Brain Research 115(1): 25-38. doi: 10.1016/s0166-4328(00)00238-2

Patterson-Kane EG, Harper DN, Hunt M (2001). The cage preferences of laboratory rats. Laboratory Animals 35(1): 74-79. doi: 10.1258/0023677011911390

Patterson-Kane EG, Hunt M, Harper D (2002). Rats demand social contact. Animal Welfare 11(3): 327-332.

Perez J and Perentes E (1994). Light-induced retinopathy in the albino rat in long-term studies: an immunohistochemical and quantitative approach. Experimental and Toxicologic Pathology 46(3): 229-235. doi: 10.1016/S0940-2993(11)80088-6

Pritchett-Corning K (2015). Rats. In: Comfortable Quarters for Laboratory Animals (Eds. Liss C, Litwak K, Tilford D, Reinhardt V), Animal Welfare Institute.

Van de Weerd H, van den Broekb FAR, Baumansaet V (1996). Preference for different types of flooring in two rat strains. Applied Animal Behaviour Science 46(3-4): 251-261. doi: 10.1016/0168-1591(95)00654-0

Vitalo AG, Gorantla S, Fricchione JG et al. (2012). Environmental enrichment with nesting material accelerates wound healing in isolation-reared rats. Behavioural Brain Research 226(2): 606-612. doi: 10.1016/j.bbr.2011.09.038