Individual Rats Research Articles

Inversely Active Striatal Projection Neurons and Interneurons Selectively Delimit Useful Behavioral Sequences

Understanding neural representations of behavioral routines is critical for understanding complex behavior in health and disease. We demonstrate here that accentuated activity of striatal projection neurons (SPNs) at the beginning and end of such behavioral repertoires is a supraordinate representation specifically marking previously rewarded behavioral sequences independent of the individual movements making up the behavior. We recorded spike activity in the striatum and primary motor cortex as individual rats learned specific rewarded lever-press sequences, each one unique to a given rat. Motor cortical neurons mainly responded in relation to specific movements regardless of their sequence of occurrence. By contrast, striatal SPN populations in each rat fired preferentially at the initiation and termination of its acquired sequence. Critically, the SPNs did not exhibit this bracketing signal when the same rats performed unreinforced sequences containing the same sub-movements that were present in their acquired sequence. Thus, the SPN activity was specifically related to a given repetitively reinforced movement sequence. This striatal beginning-and-end activity did not appear to be dependent on motor cortical inputs. However, strikingly, simultaneously recorded fast-spiking striatal interneurons (FSIs) showed equally selective but inverse firing patterns: they fired in between the initiation and termination of the acquired sequences. These findings suggest that the striatum contains networks of neurons representing acquired sequences of behavior at a level of abstraction higher than that of the individual movements making up the sequence. We propose that such SPN-FSI networks of the striatum could underlie the acquisition of chunked behavioral units.

Harnessing Population Genetics for Pest Management: Theory and Application for Urban Rats (Abstract)

Effective management of rodent pests requires an ecological understanding of how they move through their environment, and how those movements influence the invasion, persistence, or reinvasion of problematic colonies. Traditional methodologies used to describe rodent movement patterns, such as mark-recapture, are hindered by their time-consuming nature and limited geographic scope. As such, our understanding of how rodents interact with urban environments remains limited. Population genetic principles and tools have the capacity to greatly increase our understanding of rodent population dynamics, ecological relationships, and movements across space but this field is often unapproachable to non-scientist pest management professionals. In this paper we aim to promote collaborative and integrative rodent pest management by introducing relevant population genetic principles, providing examples of their applications in studies of urban brown rats, and proposing future initiatives that link scientific, private, and government entities. Using a densely-sampled brown rat population in the city of Vancouver, BC we show how genetic relationships among individual brown rats can be leveraged to understand the geographic distribution of genetic clusters (i.e., colonies), natural barriers to migration, and the spatial scale of dispersal. We describe how these results can be exploited by PMPs to directly inform the creation of management units and decrease the likelihood of rapid post-treatment reinvasion. Further, we discuss the difficulties inherent in population genetic studies and the potential for high-quality model sites to develop generalizable strategies. Overall, we hope to expand the toolbox of pest management professionals, foster collaboration, and move towards more informed and sustainable management strategies.

Individual differences in incentive salience attribution are not related to suboptimal choice in rats

Previous research has shown great variation in the extent to which individual rats attribute incentive salience to stimuli that are predictors of reinforcement. When using the Pavlovian Conditioned Approach procedure, in which a discrete stimulus is presented contingently before the delivery of reinforcement, the attribution of incentive salience is demonstrated by sign-tracking behavior (responses directed toward the stimulus predictor of reinforcement), while an absence of this attribution is reflected by goal-tracking behavior (responses directed toward the source of reinforcement). It has been reported that sign-tracking subjects have a higher tendency to perform some maladaptive behaviors than goal-tracking subjects, and that in non-classified rats, increasing the incentive salience of the stimuli promotes suboptimal choice in the “suboptimal choice procedure”. In this task, subjects are presented with two alternatives, one of them better in terms of the information provided by the discriminative stimuli, but worse in terms of probability of reinforcement (suboptimal alternative). Integrating these ideas, we hypothesized that sign-trackers would behave suboptimally, in contrast to goal-trackers. In the present study, 45 rats were classified according to their performance in the Pavlovian Conditioned Approach procedure and subjects with extreme values (sign-trackers, and goal-trackers) were evaluated in the suboptimal choice procedure. Both groups were found to behave optimally, with no differences between them. The difference between groups in capacity of attribution of incentive salience was preserved during the entire experiment, suggesting that this variable is not related to choice performance in the suboptimal choice procedure.

Syringe-feeding as a novel delivery method for accurate individual dosing of probiotics in rats.

Probiotic administration to rodents is typically achieved using oral gavage or water bottles, but both approaches may compromise animal welfare, bacterial viability, dosing accuracy, or ease of administration. Oral gavage dosing may induce stress, especially when given daily over several weeks, and cannot be performed by inexperienced personnel. Delivery in water bottles does not take multiple co-housed animals into account, leading to inaccurate dosing of individual rats. Moreover, slow consumption of the solutions over several hours may lead to variability in bacterial stability, and potential leftovers or clogging of the bottle further threaten the reliability of this method. To date, no method has been described that can provide non-stressful precise dosing of probiotics or prebiotics in individual rats. In accordance with the 3R principles (replace, reduce, refine), we propose syringe-feeding as a refinement method for simple yet accurate administration of probiotics. Animals hereby voluntarily consume the solution directly from a syringe held into their home cage, thereby enabling controlled dosing of individual animals. This method requires a short training phase of approximately 3 days, but is very fast thereafter, only taking seconds per rat. Since studies using probiotics are usually long-term experiments, we consider syringe-feeding the most appropriate probiotic delivery mode available to date.

Pharmacokinetics, disease-modifying activity, and safety of an experimental therapeutic targeting an immunological isoform of macrophage migration inhibitory factor, in rat glomerulonephritis

New therapeutic agents are needed to overcome the toxicity and suboptimal efficacy observed in current treatment of glomerulonephritis (GN). BaxB01 is a fully human monoclonal antibody targeting a disease-related immunologically distinct isoform of Macrophage migration Inhibitory Factor (MIF), designated oxidized MIF (oxMIF) and locally expressed in inflammatory conditions. We report the pharmacokinetic profile of BaxB01, and its dose and exposure-related disease-modifying activity in experimentally induced rat GN.BaxB01 bound to rat oxMIF with high affinity and reduced rat macrophage migration in vitro. After intravenous administration in rats, BaxB01 demonstrated favorable pharmacokinetics, with a half-life of up to nine days. Disease modification was dose-related (≥ 10mg/kg) as demonstrated by significantly reduced proteinuria and diminished histopathological glomerular crescent formation. Importantly, a single dose was sufficient to establish an exposure-related, anti-inflammatory milieu via amelioration of glomerular cellular inflammation. Pharmacodynamic modeling corroborated these findings, consistently predicting plasma exposures that were effective in attenuating both anti-inflammatory activity and reducing loss of kidney function. This pharmacologic benefit on glomerular function and structure was sustained during established disease, while correlation analyses confirmed a link between the antibody's anti-inflammatory activity and reduced crescent formation in individual rats. Finally, safety assessment in rats showed that the experimental therapeutic was well tolerated without signs of systemic toxicity or negative impact on kidney function.These data define therapeutically relevant exposures correlated with mechanism-based activity in GN, while toxicological evaluation suggests a large therapeutic index and provides evidence for achieving safe and effective exposure to a MIF isoform-directed therapeutic in nephritis-associated disease.

High CYP2E1 activity correlates with hepatofibrogenesis induced by nitrosamines.

Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma. The relationship between CYP2E1 innate activity and hepatofibrogenesis was evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was determined in a Sprague-Dawley rat model of diethylnitrosamine-induced hepatofibrosis. The results demonstrated that the CYP2E1 activities in human fibrotic tissues are significantly higher than that in normal liver tissues. In rats treated with diethylnitrosamine, the livers demonstrated various degree of fibrotic changes and collagen deposition in individual rats. The Ishak score, which determines the stage of fibrosis, correlated with CYP2E1 innate activity, with greater fibrosis in rat livers with higher CYP2E1 innate activity. Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis and there was an inverse correlation between the degree of inhibition and the extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for hepatofibrogenesis induced by nitrosamines.

Differential mGluR5 expression in response to the same stress causes individually adapted hippocampal network activity

Individual differences in stress vulnerability and resilience have been observed even within a single cohort of inbred rats or mice. Stress phenotypes are typically quantified as changes in the behavior of experimental animals, which is the outcome of altered electrical activity of the brain network. Although mGluR5 is associated with individual vulnerability to stress and can act as a sensitive biomarker of stress adaptation, our understanding of mGluR5-dependent modifications to neural network activities in vivo remains limited. Here, we examined individual rats for changes in hippocampal mGluR5 expression induced by restraint stress and found that these changes cause accompanying changes in hippocampal electroencephalography (EEG) activity. We found six days of restraint stress caused variable changes in hippocampal mGluR5 expression, ranging from 20.9% to 210.7% of the control group. The low mGluR5 protein group (LE) showed increased methylation of the mGluR5 CpG island, reduced mGluR5 mRNA levels, and unaltered basal EEG theta spectral power between stress day 1 and 6. In contrast, the high mGluR5 protein group (HE) showed reduced methylation of CpG sites, increased mGluR5 mRNA expression, and reduced basal theta spectral power on stress day 6. We also found that injection of lentiviruses expressing mGluR5-specific shRNAs into the hippocampus rescued this reduction in baseline theta power in HE rats. These data suggest a causal relationship between individual differences in the changes in hippocampal mGluR5 expression induced by repetitive restraint stress and the accompanying changes in ensemble neural activity in the hippocampus.

Altered understory characteristics affect rodent spatial and foraging behaviors and reproduction patterns

Understanding how changes to habitat characteristics affect behaviors is necessary to integrate biodiversity goals with land management. Managed forests are a significant landscape component in the southern United States and provide opportunities for conservation alongside production of wood products. We investigated behavioral responses of rodents to differences in understory habitat characteristics from intercropping switchgrass (Panicum virgatum), a native biofuel feedstock, in intensively managed loblolly pine (Pinus taeda) stands. Previous research indicated that planting switchgrass increased rodent population abundance but reduced recruitment and community diversity. To understand potential mechanisms underlying our previous results, we measured behaviors of individual cotton rats (Sigmodon hispidus), a grassland specialist, to planted switchgrass. We hypothesized that female territory size, foraging activity, overlap with other adult females, and reproduction indices would differ among treatments (switchgrass monocrop, intercropped switchgrass, and control plots) due to variation in grass abundance and vertical vegetation cover. We conducted live-trapping, radio telemetry, and foraging activity surveys on cotton rats during summers of 2013–2015. We found no treatment effect on territory size, but foraging activity was 2 times higher in monocrop than control plots. We also found a positive relationship between female spatial overlap and percentage of grass in control plots and evidence for higher reproductive indices in control than monocrop plots. Our results suggest that cotton rats in monocrop plots exhibited unexpected behaviors, and monocrop plots may serve as population sinks with low rodent diversity. Overall, results from this replicated experiment suggested that intercropping provides adequate food and cover to maintain rodent populations and produce forest products.

Blood flow, volume and arterio-venous passages in induced mammary tumours of the rat

ObjectiveTo study blood flow, vascular volume and arterio-venous passages in induced mammary tumours of the rat to characterize parameters possibly responsible for tumour hyponutrition. MethodDimethylbenzanthracene-induced mammary tumours in Sprague-Dawley rats were studied. Regional blood flow was studied by use of the radioactive microsphere tracer technique using 141Cerium-labelled 15μm spheres coinjected into the left cardiac ventricle with 125Iodine-labelled 25μm spheres. Blood volume was studied by use of 125Iodine- or 99mTechnetium-labelled human serum albumin, the latter allowing autoradiography of tumour sections for visualization of flow and volume. ResultsTwenty-seven rats with 170 tumours had a mean tumour blood flow of 48 and 67mL×min−1×100g−1 using 15 and 25μm sphere data, respectively, indicating a significant passage through vessels between 15 and 25μm. The lungs showed a “nominal bronchial” blood flow of 260 and 135mL×min−1×100g−1 for the 15 and 25μm spheres, respectively, indicating pulmonary trapping, particularly of small spheres passing the systemic circulation in vessels larger than 15μm. There was a positive correlation between the total tumour blood flow within individual rats and trapped spheres of both dimensions in the lungs, indicating shunts also larger than 25μm.Normal tissues disclosed only small differences in regional blood flow as measured by the two spheres.Blood volume was studied in 20 rats with 120 tumours, with a vascular volume of 3.6mL×100g−1 representing a blood turnover >15 times/min. Blood volume co-localized with perfusion as seen in autoradiographs. ConclusionIn induced rat mammary tumours, a high fraction of blood, 28%, passes arterio-venous vessels between 15 and 25μm and there also exist passages >25μm. These findings indicate that the functional capacity of the tumour vascular bed might be impaired, adding to the abnormal microenvironment of tumours.

Automated recording of home cage activity and temperature of individual rats housed in social groups: The Rodent Big Brother project.

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery.

Spontaneous testicular atrophy occurs despite normal spermatogonial proliferation in a Tp53 knockout rat.

The tumor suppressor protein p53 (TP53) has many functions in cell cycle regulation, apoptosis, and DNA damage repair and is also involved in spermatogenesis in the mouse. To evaluate the role of p53 in spermatogenesis in the rat, we characterized testis biology in adult males of a novel p53 knockout rat (SD-Tp53tm1sage ). p53 knockout rats exhibited variable levels of testicular atrophy, including significantly decreased testis weights, atrophic seminiferous tubules, decreased seminiferous tubule diameter, and elevated spermatocyte TUNEL labeling rates, indicating a dysfunction in spermatogenesis. Phosphorylated histone H2AX protein levels and distribution were similar in the non-atrophic seminiferous tubules of both genotypes, showing evidence of pre-synaptic DNA double-strand breaks in leptotene and zygotene spermatocytes, preceding cell death in p53 knockout rat testes. Quantification of the spermatogonial stem cell (SSC) proliferation rate with bromodeoxyuridine (BrdU) labeling, in addition to staining with the undifferentiated type A spermatogonial marker GDNF family receptor alpha-1 (GFRA1), indicated that the undifferentiated spermatogonial population was normal in p53 knockout rats. Following exposure to 0.5 or 5 Gy X-ray, p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild-type rat testes was elevated to a level similar to the unexposed p53 knockout rats. This study indicates that seminiferous tubule atrophy occurs following spontaneous, elevated levels of spermatocyte death in the p53 knockout rat. This phenomenon is variable across individual rats. These results indicate a critical role for p53 in rat germ cell survival and spermatogenesis.

Locus coeruleus neuronal activity correlates with behavioral response to acute and chronic doses of methylphenidate (Ritalin) in adolescent rats.

The objective of this study is to gain insight into the behavioral and neuronal changes induced by acute and chronic methylphenidate (MPD) administration. Specifically, there is limited knowledge of the effects of MPD on the locus coeruleus (LC), the main site of norepinephrine synthesis in the brain. In this study, LC neuronal firing rate was recorded simultaneously with locomotor activity in freely moving adolescent rats. Adolescent rats were chosen to mimic the age group in humans most affected by MPD exposure. Following acute dose of 0.6, 2.5 or 10mg/kg MPD, all rats showed an increase in locomotor activity. However, in response to chronic MPD doses, individual rats showed either a further increase or decrease in their locomotor activity as compared to the effect initiated by the acute dose-expressing either behavioral sensitization or tolerance, respectively. The LC neuronal recordings from animals expressing behavioral sensitization showed that the majority of units responded to chronic MPD exposure by further increasing firing rates as compared to the initial response to the acute MPD exposure. For the LC neuronal units recorded from animals expressing behavioral tolerance, however, the majority of the units responded to chronic exposure by attenuating or no significant effect on their firing rate as compared to the acute MPD exposure. This observation indicates a correlation between the LC neuronal responses and behavioral activity to chronic MPD exposure. The study shows that LC participates in the effect of MPD and the behavioral expression of sensitization and tolerance to chronic exposure of MPD.

Reinforcement learning models of risky choice and the promotion of risk-taking by losses disguised as wins in rats.

Risky decisions are inherently characterized by the potential to receive gains or incur losses, and these outcomes have distinct effects on subsequent decision-making. One important factor is that individuals engage in loss-chasing, in which the reception of a loss is followed by relatively increased risk-taking. Unfortunately, the mechanisms of loss-chasing are poorly understood, despite the potential importance for understanding pathological choice behavior. The goal of the present experiment was to illuminate the mechanisms governing individual differences in loss-chasing and risky-choice behaviors. Rats chose between a low-uncertainty outcome that always delivered a variable amount of reward and a high-uncertainty outcome that probabilistically delivered reward. Loss-processing and loss-chasing were assessed in the context of losses disguised as wins (LDWs), which are loss outcomes that are presented along with gain-related stimuli. LDWs have been suggested to interfere with adaptive decision-making in humans and thus potentially increase loss-making. Here, the rats presented with LDWs were riskier, in that they made more choices for the high-uncertainty outcome. A series of nonlinear models were fit to individual rats' data to elucidate the possible psychological mechanisms that best account for individual differences in high-uncertainty choices and loss-chasing behaviors. The models suggested that the rats presented with LDWs were more prone to showing a stay bias following high-uncertainty outcomes compared to rats not presented with LDWs. These results collectively suggest that LDWs acquire conditioned reinforcement properties that encourage continued risk-taking and increase loss-chasing following previous high-risk decisions. (PsycINFO Database Record

Automated recording of home cage activity and temperature of individual rats housed in social groups: the Rodent Big Brother project

Automated recording of home cage activity and temperature of individual rats housed in social groups: the Rodent Big Brother project

К вопросу о гельминтах серых крыс города Омска

Gray rat is one of the many species of rodents, prone to Sinanthropus, omnivorous and rapid fertility. Living in close proximity to human, rats are a real danger to people, because they can serve as reservoirs and sources of pathogens of various diseases of viral, bacterial and parasitic nature. Infection of human occurs through direct contact with the corpses of the fallen within the dwelling rats, food, contaminated by their faeces, through surfaces, that come into contact with sick animals, and indirectly through domestic cats and dogs. The study of gray rat’s helminthofauna is one of the important tasks in the assessment of helminth infections spread in Omsk. The aim is to study the species composition of gray rats helminths in Omsk. Objectives are: to determine the species composition of gray rats helminths; set the extensiveness of (E.I.) and intensity (I.I.) of invasions. The charges of helminths from 18 rats were materials for their own research. Catching rats was carried out on the territory of clinical hospital of the building 2 of Institute of Veterinary Medicine of Omsk State Agrarian University name after P.A. Stolypin. An autopsy was carried out in rats according to the procedure for opening the helminthological full of K.I. Skryabin. Total helminths infestation of gray rats was 100%. 3 types of helminths were revealed in 18 individual gray rats. Among cestodes the Hymenolepis diminutive is widely distributed in the form of gray rats. The extensiveness invasion is 55.5%, with an average intensity of 4 units. Cestodes Rodentolepis straminea infected 33.3% of rodents with intensity of 5 units. Syphacia muris nematode was found in 33.3% of the individuals, the intensity of infection was 2.6 units. The findings have important economic significance and should be considered in the prevention work of veterinary, sanitary - epidemiological and health services.

Rotula Aquatica Lour Aqueous Extract as Anti-Urolithiatic Agent in Experimentally Induced Urolithiatic Rat Model

Rotula aquatica Lour is traditionally used to regulate the kidney and bladder stones and root decoction is used for diuretic activity. The present study was carried out to assess the antiurolithiatic activity of the aqueous root extract of the plant in urolithiatic rats.The extract was administered to the calcium oxalate (CaOx) urolithiatic rats orally at 100 and 200 mg/kg body weight along with ethylene glycol (EG) for 28 days. On 28 day, 24 h urine was collected from individual rats and urine was analysed for protein, calcium, phosphate, magnesium, uric acid, oxalate and creatinine. On same day the serum protein, calcium, phosphate, magnesium, uric acid, oxalate, creatinine and blood urea nitrogen levels were also estimated in each animal. The kidney homogenate was used for the estimation of calcium, oxalate and phosphate. The paraffin kidney sections were prepared to observe the CaOx deposits. The paraffin kidney sections showed significant histopathological changes. The treatment with aqueous root extract of Rotula aquatica at 100 and 200 mg/kg body weight doses significantly decreased the urine protein, calcium, phosphate, uric acid, creatinine and oxalate, serum protein, calcium, phosphate, uric acid, creatinine, blood urea nitrogen and oxalate and renal tissues calcium, phosphate and oxalate, in EG induced urolithiasis after 28 days.The present study indicated aqueous root extract of Rotula aquatica at the dose of 200 mg/kg body weight as more effective in decreasing the urolithiasis and regeneration of renal tissues in male rats. The extract has a potential to cure the urolithiasis.

Rodent age-related impairments in discriminating perceptually similar objects parallel those observed in humans.

The ability to accurately remember distinct episodes is supported by high-level sensory discrimination. Performance on mnemonic similarity tasks, which test high-level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical-hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross-characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical-hippocampal circuit dysfunction in aging and disease.

Abuse‐Related Effects of “Bath Salts” Mixtures: Studies with MDPV, Methylone, and Caffeine in Rats.

The recreational use of synthetic cathinones has become a serious public health problem worldwide. In the US, “bath salts” products often contain MDPV (a monoamine transporter inhibitor) or methylone (a monoamine transporter substrate); however, preparations often contain mixtures of multiple synthetic cathinones, or mixtures of a synthetic cathinone and caffeine. In order to determine if the reinforcing effects of mixtures of “bath salts” constituents differed from the reinforcing effects of the constituents alone, adult male Sprague Dawley rats were trained to self‐administer either 0.032 mg/kg/inf MDPV or 0.32 mg/kg/inf methylone under a progressive ratio (PR) schedule of reinforcement. Drug mixtures were based on the concept of dose equivalence, with each pair of drugs evaluated at three ratios (3:1, 1:1, and 1:3) relative to the mean ED50 for each drug. Dose addition analyses were used to calculate predicted effect levels for an additive interaction at each dose pair of each combination of drugs using the Emax, ED50, and slope parameters derived from dose‐response curves obtained in individual rats. Although high levels of responding were maintained by each of the “bath salts” mixtures, the nature of the interaction varied depending upon the constituent drugs. For combinations containing a cathinone and caffeine (MDPV+caffeine and methylone+caffeine), the interactions were generally additive, however, when mixed at a 3:1 ratio of their ED50s the reinforcing effects of both sets of mixtures were found to be supra‐additive. Interestingly, although combining caffeine with MDPV appeared to only increase the potency of the mixture, combining caffeine and methylone significantly increased the reinforcing effectiveness of the a “bath salts” mixture beyond that which would be predicted for an additive interaction. Unlike with combinations of cathinones and caffeine, when MDPV was combined with methylone departures from additivity tended to occur in the sub‐additive direction, with the onset of toxicity observed with larger dose pairs of the MDPV+methylone mixtures. Together, these studies suggest that the reinforcing effects of binary mixtures containing common bath salts constituents (i.e., MDPV, methylone, and caffeine) are generally additive in nature; however, both supra‐additive (MDPV+caffeine and methylone+caffeine) and sub‐additive interactions (MDPV+methylone) can be observed. Although such interactions could account for the high rates of bath salts abuse, further study will be needed to determine if similar interactions exist between these and other bath salts constituents with regard to other abuse‐related and toxic effects.Support or Funding InformationThis study was supported by a National Institutes of Health (NIH) research grant (R01 DA039146) from the National Institute on Drug Abuse (NIDA), as well as the NIH Intramural Research Programs of NIDA and National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Behavioural correlates of group size and group persistence in the African ice rat Otomys sloggetti robertsi

The relationship between group size and fitness has attracted much interest, with many attempts made to detect an optimal group size. Group size is determined by the benefits and costs influencing group formation, which also influences whether groups persist or fail. We investigated whether group size is associated with success (individual survival and reproductive output) in the African ice rat Otomys sloggetti robertsi. Ice rats form mixed-sex plural-breeding colonies that trade off the benefits of huddling below-ground against within-colony resource competition above-ground. We measured behavioural correlates of individual success in summer and winter, focusing on energy saving (basking), acquisition (foraging) and use (burrow maintenance, distance travelled for foraging) behaviours. We predicted that (1) individuals in larger colonies would forage and travel more to find food because of greater within-colony competition for resources; (2) individuals in larger colonies would bask less than individuals in smaller colonies because of the greater energy savings generated from huddling in larger groups; and (3) burrow maintenance would be greater in smaller colonies because of fewer individuals engaging in this task. We showed that colonies succumbed or persisted as a group (i.e. most individuals present or all absent). In particular, in both seasons, individuals in smaller groups (≤5 individuals) were more likely to fail, while those in larger groups (≥12 individuals) were more likely to persist. The persistence of colonies was positively predicted by foraging and negatively by basking. Foraging was greater in larger colonies and burrow maintenance was greater in smaller colonies. While females of larger colonies produced more offspring in total, reproductive output (per capita offspring production) was not correlated with colony size. Individual ice rats in larger colonies accrued fitness benefits, which were predicted, proximally, by greater foraging and possibly energy savings in larger huddling groups. What proximally determines the relationship between group size, individual success and colony persistence? In ice rats, individuals in larger groups persist, which is correlated with more foraging. Larger groups possibly enjoy the benefits of huddling in larger groups, which are re-channelled into energy-intense activities. Groups failed or persisted as a unit. Investigating the behavioural correlates of the relationship between group size and persistence provides insight into the proximal underpinnings of this relationship.

Individual Differences in Male Rats in a Behavioral Test Battery: A Multivariate Statistical Approach.

Animal models for anxiety, depressive-like and cognitive diseases or aging often involve testing of subjects in behavioral test batteries. The large number of test variables with different mean variations and within and between test correlations often constitute a significant problem in determining essential variables to assess behavioral patterns and their variation in individual animals as well as appropriate statistical treatment. Therefore, we applied a multivariate approach (principal component analysis) to analyse the behavioral data of 162 male adult Sprague-Dawley rats that underwent a behavioral test battery including commonly used tests for spatial learning and memory (holeboard) and different behavioral patterns (open field, elevated plus maze, forced swim test) as well as for motor abilities (Rota rod). The high dimensional behavioral results were reduced to fewer components associated with spatial cognition, general activity, anxiety-, and depression-like behavior and motor ability. The loading scores of individual rats on these different components allow an assessment and the distribution of individual features in a population of animals. The reduced number of components can be used also for statistical calculations like appropriate sample sizes for valid discriminations between experimental groups, which otherwise have to be done on each variable. Because the animals were intact, untreated and experimentally naïve the results reflect trait patterns of behavior and thus individuality. The distribution of animals with high or low levels of anxiety, depressive-like behavior, general activity and cognitive features in a local population provides information of the probability of their appeareance in experimental samples and thus may help to avoid biases. However, such an analysis initially requires a large cohort of animals in order to gain a valid assessment.