Judgement bias in pigs is independent of performance in a spatial holeboard task and conditional discrimination learning.

Biases in judgement of ambiguous stimuli, as measured in a judgement bias task, have been proposed as a measure of the valence of affective states in animals. We recently suggested a list of criteria for behavioural tests of emotion, one of them stating that responses on the task used to assess emotionality should not be confounded by, among others, differences in learning capacity, i.e. must not simply reflect the cognitive capacity of an animal. We performed three independent studies in which pigs acquired a spatial holeboard task, a free choice maze which simultaneously assesses working memory and reference memory. Next, pigs learned a conditional discrimination between auditory stimuli predicting a large or small reward, a prerequisite for assessment of judgement bias. Once pigs had acquired the conditional discrimination task, optimistic responses to previously unheard ambiguous stimuli were measured in the judgement bias task as choices indicating expectation of the large reward. We found that optimism in the judgement bias task was independent of all three measures of learning and memory indicating that the performance is not dependent on the pig's cognitive abilities. These results support the use of biases in judgement as proxy indicators of emotional valence in animals.

Effects of environmental enrichment on cognitive performance of pigs in a spatial holeboard discrimination task.

This study investigated the effects of environmental enrichment on the cognitive performance of female conventional farm (growing) pigs in a spatial holeboard task. Ten pairs of littermates matched for weight were used. From each litter, one piglet was randomly assigned to a barren environment; the other was assigned to an enriched environment from 4 weeks of age. The enriched environment was double the size of the barren environment, had a floor covered with straw, a rooting area filled with peat, and one of the four different enrichment toys which were exchanged daily. Starting at 11 weeks of age, all pigs were tested in a spatial holeboard discrimination task in which 4 out of 16 holes were baited. Furthermore, basal salivary cortisol levels of all pigs were determined after the end of all testing. All pigs were able to acquire the pattern of baited holes (acquisition phase, 40 trials) and the diagonally mirrored pattern (reversal phase, 20 trials). During the acquisition phase, the reference memory performance of the enriched-housed pigs was better than that of their barren-housed littermates, i.e. they reduced visits to the unbaited set of holes. During the reversal phase, enriched-housed pigs had a better general working memory performance than the barren-housed pigs as indicated by reduced revisits to holes already visited during a trial, irrespective of whether they were of the baited or the unbaited set. The enriched-housed pigs also searched for the hidden bait faster during both phases. The environments did not affect basal salivary cortisol levels. In conclusion, environmental enrichment slightly improved the cognitive performance of pigs in a spatial learning task. We hypothesise that the long period of habituation to and testing in the holeboard acted as enrichment that partially reduced the effects of barren housing.

Tolerability and efficacy of the intestinal phosphate binder Lantharenol® in cats.

BACKGROUND: Tolerability and efficacy of the intestinal phosphate binder Lantharenol® (lanthanum carbonate octahydrate) were tested in two prospective, randomized and negative controlled laboratory studies with healthy adult cats fed commercial maintenance diets non-restricted in phosphorus. In the first study, the maximal tolerated dose was determined. Starting from a dose of 0.125 g/kg body weight mixed with the daily feed ration, the dose of Lantharenol® was doubled every other week until signs of intolerability were observed (N=10 cats compared to 5 untreated controls). In the second study, the effects of feed supplementation for two weeks with approximately 2, 6, and 20% of the maximal tolerated dose on phosphorus excretion patterns and balance were assessed (N=8 cats per group). RESULTS: Lantharenol® was found to be safe and well tolerated up to the dose of 1 g/kg bodyweight, corresponding to a concentration of 84 g Lantharenol®/kg complete feed, defined as dry matter with a standard moisture content of 12%. Feed supplementation for two weeks with approximately 2-20% of this dosage (i.e., 1.6, 4.8, and 16 g/kg complete feed) resulted in a shift from urinary to faecal phosphorus excretion. Apparent phosphorus digestibility was dose-dependently reduced compared to the control group fed with diet only (N=8). CONCLUSIONS: The feed additive was well accepted and tolerated by all cats. Therefore, Lantharenol® presents a well tolerated and efficacious option to individually tailor restriction of dietary phosphorus as indicated, for instance, in feline chronic kidney disease.

Glucocorticoids in relation to behavior, morphology, and physiology as proxy indicators for the assessment of animal welfare. A systematic mapping review.

Translating theoretical concepts of animal welfare into quantitative assessment protocols is an ongoing challenge. Glucocorticoids (GCs) are frequently used as physiological measure in welfare assessment. The interpretation of levels of GCs and especially their relation to welfare, however, is not as straightforward, questioning the informative power of GCs. The aim of this systematic mapping review was therefore to provide an overview of the relevant literature to identify global patterns in studies using GCs as proxy for the assessment of welfare of vertebrate species. Following a systematic protocol and a-priory inclusion criteria, 509 studies with 517 experiments were selected for data extraction. The outcome of the experiments was categorized based on whether the intervention significantly affected levels of GCs, and whether these effects were accompanied by changes in behavior, morphology and physiology. Additional information, such as animal species, type of intervention, experimental set up and sample type used for GC determination was extracted, as well. Given the broad scope and large variation in included experiments, meta-analyses were not performed, but outcomes are presented to encourage further, in-depth analyses of the data set. The interventions did not consistently lead to changes in GCs with respect to the original authors hypothesis. Changes in GCs were not consistently paralleled by changes in additional assessment parameter on behavior, morphology and physiology. The minority of experiment quantified GCs in less invasive sample matrices compared to blood. Interventions showed a large variability, and species such as fish were underrepresented, especially in the assessment of behavior. The inconclusive effects on GCs and additional assessment parameter urges for further validation of techniques and welfare proxies. Several conceptual and technical challenges need to be met to create standardized and robust welfare assessment protocols and to determine the role of GCs herein.

Beneficial effects of a plant-fish oil, slow carbohydrate diet on cardio-metabolic health exceed the correcting effects of metformin-pioglitazone in diabetic pigs fed a fast-food diet.

BACKGROUND: Lifestyle influences endocrine, metabolic and cardiovascular homeostasis. This study investigated the impact of diet and oral anti-diabetic medication on cardio-metabolic health in human-sized diabetic pigs. METHODS: After a growing pre-phase from ~30 to ~69 kg during which domestic pigs were fed either a low fat, low sucrose diet (group A) or a fast food-type diet elevated in lard (15%) and sucrose (40%) (group B), the pigs were subdivided in 5 groups (n = 7-8 pigs per group). Group 1, normal pigs from group A on a low fat, low sugar (L) pig diet and group 2, normal pigs from group B on a high lard (25%), sucrose-fructose (40%), cholesterol (1%) fast food-type (F) diet. Diabetes (D) was induced in group B pigs by streptozotocin and group 3 received the F diet (DF), group 4 received the F diet with Anti-diabetic medication metformin (2 g.day-1)-pioglitazone (40 mg.day-1) (DFA) and group 5 switched to a Plant-Fish oil (25%), Slowly digestible starch (40%) diet (DPFS). The F and PFS diets were identical for fat, carbohydrate and protein content but only differed in fat and carbohydrate composition. The 5 pig groups were followed up for 7 weeks until reaching ~120 kg. RESULTS: In normal pigs, the F diet predisposed to several abnormalities related to metabolic syndrome. Diabetes amplified the inflammatory and cardiometabolic abnormalities of the F diet, but both oral FA medication and the PFS diet partially corrected these abnormalities (mean±SEM) as follows: Fasting plasma TNF-ɑ (pg.ml-1) and NEFA (mmol.l-1) concentrations were high (p<0.02) in DF (193±55 and 0.79±0.16), intermediate in DFA (136±40 and 0.57±012) and low in DPFS pigs (107±31 and 0.48±0.19). Meal intolerance (response over fasting) for glucose and triglycerides (area under the curve, mmol.h-1) and for lactate (3-h postprandial, mmol.l-1) was high (p<0.03) in DF (489±131, 8.6±4.8 and 2.2±0.6), intermediate in DFA (276±145, 1.4±1.1 and 1.6±0.4) and low in DPFS (184±62, 0.7±1.8 and 0.1±0.1). Insulin-mediated glucose disposal (mg.kg-1.min-1) showed a numerical trend (p = NS): low in DF (6.9±2.2), intermediate in DFA (8.2±1.3) and high in DPFS pigs (10.4±2.7). Liver weight (g.kg-1 body weight) and liver triglyceride concentration (g.kg-1 liver) were high (p<0.001) in DF (23.8±2.0 and 69±14), intermediate in DFA (21.1±2.0 and 49±15) and low in DPFS pigs (16.4±0.7 and 13±2.0). Aorta fatty streaks were high (p<0.01) in DF (16.4±5.7%), intermediate in DFA (7.4±4.5%) and low in DPFS pigs (0.05±0.02%). CONCLUSION: This translational study using pigs with induced type 2 diabetes provides evidence that a change in nutritional life style from fast food to a plant-fish oil, slowly digestible starch diet can be more effective than sole anti-diabetic medication.

Evaluation of animal models of neurobehavioral disorders.

Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration.Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended) replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result.Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia.In a manner congruent to that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s) of a model and by defining better evaluation criteria, based on the proposed use of the model.

Emotional reactivity and cognitive performance in aversively motivated tasks: a comparison between four rat strains.

BACKGROUND: Cognitive function might be affected by the subjects' emotional reactivity. We assessed whether behavior in different tests of emotional reactivity is correlated with performance in aversively motivated learning tasks, using four strains of rats generally considered to have a different emotional reactivity. METHODS: The performance of male Brown Norway, Lewis, Fischer 344, and Wistar Kyoto rats in open field (OF), elevated plus-maze (EPM), and circular light-dark preference box (cLDB) tasks, which are believed to provide measures of emotional reactivity, was evaluated. Spatial working and reference memory were assessed in two aversively motivated learning and memory tasks: the standard and the "repeated acquisition" versions of the Morris water maze escape task, respectively. All rats were also tested in a passive avoidance task. At the end of the study, levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid, and 5-HT turnover in the hippocampus and frontal cortex were determined. RESULTS: Strain differences showed a complex pattern across behavioral tests and serotonergic measures. Fischer 344 rats had the poorest performance in both versions of the Morris water escape task, whereas Brown Norway rats performed these tasks very well but the passive avoidance task poorly. Neither correlation analysis nor principal component analysis provided convincing support for the notion that OF, EPM, and cLDB tasks measure the same underlying trait. CONCLUSIONS: Our findings do not support the hypothesis that the level of emotional reactivity modulates cognitive performance in aversively motivated tasks. Concepts such as "emotional reactivity" and "learning and memory" cannot adequately be tapped with only one behavioral test. Our results emphasize the need for multiple testing.

The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents.

The present study investigated the putative pro-cognitive effects of the novel selective PDE9 inhibitor BAY 73-6691. The effects on basal synaptic transmission and long-term potentiation (LTP) were investigated in rat hippocampal slices. Pro-cognitive effects were assessed in a series of learning and memory tasks using rodents as subjects. BAY 73-6691 had no effect on basal synaptic transmission in hippocampal slices prepared from young adult (7- to 8-week-old) Wistar rats. A dose of 10 microM, but not 30 microM, BAY 73-6691 enhanced early LTP after weak tetanic stimulation. The dose effective in young adult Wistar rats did not affect LTP in hippocampal slices prepared from young (7- to 8-week-old) Fischer 344 X Brown Norway (FBNF1) rats, probably reflecting strain differences. However, it increased basal synaptic transmission and enhanced early LTP after weak tetanic stimulation in hippocampal slices prepared from very old (31- to 35-month-old) FBNF1 rats. BAY 73-6691 enhanced acquisition, consolidation, and retention of long-term memory (LTM) in a social recognition task and tended to enhance LTM in an object recognition task. Bay 73-6691 attenuated the scoplamine-induced retention deficit in a passive avoidance task, and the MK-801-induced short-term memory deficits in a T-maze alternation task. The mechanism of action, possibly through modulation of the NO/cGMP-PKG/CREB pathway, is discussed. Our findings support the notion that PDE9 inhibition may be a novel target for treating memory deficits that are associated with aging and neurodegenerative disorders such as Alzheimer's disease.

Pathological anxiety in animals.

Selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a consequence, compromise welfare and quality of life. In this review it is proposed that various behavioural dysfunctions in animals are due to pathological anxiety. Although several approaches have been undertaken to specify the diagnostic criteria of pathological anxiety as a behavioural disorder in animals, the causal aetiology largely remains unknown. This is mainly due to the fact that integrated concepts, combining the behavioural syndrome and (neuro-) physiological processes, are widely lacking. Moreover, even the term anxiety itself represents a poorly defined concept or category. A definition is suggested and the potential causes of pathological anxiety are explored with a plea for developing adequate diagnostic tools and therapies to fight pathological anxiety in animals based on insight from scientific research.

Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors.

The present study investigated the time-dependent memory enhancing properties of three selective phosphodiesterase inhibitors (PDE-I) vardenafil (PDE5-I), rolipram (PDE4-I) and BAY 60-7550 (PDE2-I) in the object recognition task. In particular, the time-dependent involvement of cAMP and cGMP in memory consolidation was assessed by altering the time points of drug administration. Vardenafil (1 mg/kg, p.o.), rolipram (0.03 mg/kg, i.p.), and BAY 60-7550 (3 mg/kg, p.o.) were tested in rats with a 24 h delay between the learning and the test trial. The PDE-Is were administered at different time points, i.e. directly after, 1 h, 3 h and 6 h after the first trial. Using a 24 h interval, vardenafil only showed an effect on object memory when injected directly after trial 1, rolipram only showed an improvement when injected 3 h after trial 1 and BAY 60-7550 improved memory when injected either directly after or 3 h after trial 1. No treatment effects were found when the compounds were administered 1 h or 6 h after the first trial. Our results extend our previous data that different types of PDE-Is affect different stages of memory consolidation. Moreover, the present study provides further support that selective PDE-Is can influence memory consolidation in a time-dependent manner, assumingly by elevating central cAMP and cGMP levels.

Animal models of behavioral dysfunctions: basic concepts and classifications, and an evaluation strategy.

In behavioral neurosciences, such as neurobiology and biopsychology, animal models make it possible to investigate brain-behavior relations, with the aim of gaining insight into normal and abnormal human behavior and its underlying neuronal and neuroendocrinological processes. Different types of animal models of behavioral dysfunctions are reviewed in this article. In order to determine the precise criteria that an animal model should fulfill, experts from different fields must define the desired characteristics of that model at the neuropathologic and behavioral level. The list of characteristics depends on the purpose of the model. The phenotype-abnormal behavior or behavioral dysfunctions-has to be translated into testable measures in animal experiments. It is essential to standardize rearing, housing, and testing conditions, and to evaluate the reliability, validity (primarily predictive and construct validity), and biological or clinical relevance of putative animal models of human behavioral dysfunctions. This evaluation, guided by a systematic strategy, is central to the development of a model. The necessity of animal models and the responsible use of animals in research are discussed briefly.

Two months makes a difference in spatial orientation learning in very old FBNF1 rats.

Age-related changes in cognitive performance may be more pronounced in the period near or exceeding the median life span. Therefore, we compared the acquisition of a Morris water escape task by two groups of very old Fischer344 x Brown Norway hybrid rats. The mean age difference between the two groups of rats (a 33- to 34-month-old group versus a 35- to 36-month-old group) was about 2 months. Both groups of rats initially had the same level of performance, but then the younger group learned to escape onto the submerged platform faster, swimming a shorter distance, than the older group. By the fifth acquisition session, the younger rats needed only half the time and swam a shorter distance before they reached the platform than the older rats. These differences in learning were not due to different locomotor abilities as both groups had a similar swimming speed. These results suggest that age-related changes in cognitive performance are indeed more pronounced in the period around the median life span. We also discussed different set-ups to perform cross-sectional age-comparison studies. If there are not sufficient animals from one batch, it may be worthwhile to combine animals from different batches per age group, provided that breeding, rearing, housing, and testing conditions are highly standardized.

Effects of the cholinesterase inhibitors donepezil and metrifonate on scopolamine-induced impairments in the spatial cone field orientation task in rats.

The aim of these experiments was to assess whether the clinically validated cognition enhancers donepezil (Aricept, E2020) and metrifonate antagonize scopolamine-induced deficits in the cone field, a complex spatial discrimination task. The cone field task allows measurement of the effects of experimental manipulations on working and reference memory (WM and RM), search strategies, and on the speed and latency to execute the task. The effects of a single administration of donepezil (0.1, 0.3, and 1.0 mg kg(-1), p.o.) and metrifonate (30, 60, and 120 mg kg(-1), p.o.) were investigated in adult Harlan-Wistar rats trained to a stable level of performance and pretreated with scopolamine (0.5 mg kg(-1), i.p. 30 min before training). Scopolamine impaired WM without inducing overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine-induced deficits, whereas metrifonate antagonized the WM deficits at the dose of 60 mg kg(-1), but not at 30 or 120 mg kg(-1). Thus, a cholinesterase inhibitor with proven clinical efficacy can antagonize scopolamine-induced spatial memory deficits. The cone field would be a useful component of a behavioral screening battery to test the effects of putative cognition enhancers.

Rats with scopolamine- or MK-801-induced spatial discrimination deficits in the cone field task: animal models for impaired spatial orientation performance.

Spatial cognition appears to be compromised in elderly and in patients suffering from dementia. These deficits are believed to be modelled, at least partly, by the administration of scopolamine or MK-801 in normal adult animals. In order to establish an animal model suited for the evaluation of putative cognition enhancers, we assessed the effects of scopolamine (0.3, 0.5, 0.7 mg kg(-1), i.p.) and MK-801 (0.07, 0.08, 0.09 mg kg(-1), s.c.) in rats trained in the cone field. This task allows the simultaneous investigation of working memory (WM), reference memory (RM) and search strategies. Scopolamine and MK-801 reliably induced spatial cognition deficits in the cone field without inducing behavioural side effects. This task appears to be suited for assessing the effects of putative cognition-enhancing compounds on spatial cognition.

Overnight Social Isolation in Pigs Decreases Salivary Cortisol but Does Not Impair Spatial Learning and Memory or Performance in a Decision-Making Task.

Pigs in modern farming practice may be exposed to a number of stressors, including social stressors such as mixing or isolation. This may potentially affect both cognitive abilities and stress physiology of the animals. We tested the hypothesis that overnight social isolation in pigs impairs performance in a cognitive holeboard (HB) task (Experiment 1) and the Pig Gambling Task (PGT) (Experiment 2), a decision-making task inspired by the Iowa Gambling Task. In addition, we tested the effect of overnight social isolation on salivary cortisol levels. A within-subjects approach was used in which performance in the two behavioral tasks and cortisol levels were first determined during normal social housing, followed by performance and cortisol levels after experiencing stress induced by overnight social isolation. A total of 19 female pigs with a birth weight closest to their respective litter average was selected from 10 different litters and placed in two pens after weaning. Following habituation, pigs were trained in the HB task, starting at 10 weeks of age. Then, the pigs were isolated overnight, five individuals per night, at 15, 16, and 17 weeks of age. Between these three isolations, social housing and training in the HB continued. Starting 6 weeks after the end of the HB experiment, at approximately 23 weeks of age, the pigs were trained in the PGT. The effects of overnight social isolation on performance in this task were assessed once, when the pigs were 25 weeks old. Salivary cortisol was measured from samples collected 15 min after the start of isolation and at the end of the isolation period and compared to baseline values collected before the start of social isolation. Our results did not confirm the hypothesis that isolation impaired HB performance and decision-making in the PGT. Unexpectedly, overnight social isolation decreased cortisol levels below baseline values, an effect that was not associated with changes in performance of the behavioral tasks. We hypothesized that the housing and testing conditions may have prepared the animals to cope efficiently with stress.

Assessment of age-associated cognitive deficits in rats: a tricky business.

Every living organism is affected by changes as a consequence of aging. Perhaps the most appropriate concept to describe age-related changes is that of 'functional age'. Laboratory rodents are especially suited as models of cognitive aging in humans, because they have a relatively short life-span and because many tests have been developed to investigate their cognitive performance. Examples from studies using the Morris water escape task were chosen to describe and discuss factors which must be considered before drawing conclusions about age-related cognitive deficits. In particular, the roles of rearing and housing conditions, of sensorimotor impairments, and of motivational differences between young and old rats are discussed. Conclusions are drawn about how aging studies should be conceived and performed.

Delayed non-matching to position performance in aged hybrid Fischer 344 x brown Norway rats: a longitudinal study.

In this study, the effects of aging on the performance in a delayed non-matching to position (DNMTP) task were investigated longitudinally in hybrid Fischer 344 x Brown Norway rats. The rats were first trained to perform the task. Subsequently, their performance was assessed monthly from 28 to 34 months of age. The measures of responding on the DNMTP schedule did not decrease in the course of the study. After the last DNMTP test, choline acetyltransferase (ChAT) activity and glial fibrillary acidic protein (GFAP) content were measured in frontal cortex and hippocampus. We found that higher levels of GFAP in the frontal cortex, but not hippocampus, were associated with a poorer performance in the DNMTP task. Our findings support the notion that repeated testing prevents the age-related decline in cognitive functions that has been reported in cross-sectional studies. Pathology of the frontal cortex seems to predict a faster rate of forgetting in aging rats.

Pharmacological and behavioral profile of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141), a novel α7 nicotinic acetylcholine receptor agonist/serotonin 5-HT3 receptor antagonist.

RATIONALE AND OBJECTIVE: Agonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/serotonin 5-HT3 receptor (5-HT3R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects. RESULTS: EVP-5141 bound to α7 nAChRs in rat brain membranes (K i = 270 nM) and to recombinant human serotonin 5-HT3Rs (K i = 880 nM) but had low affinity for α4ß2 nAChRs (K i > 100 µM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT3R antagonist but did not block α3ß4, α4ß2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg(-1), p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg(-1)) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg(-1), p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg(-1), i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg(-1), p.o.). CONCLUSIONS: EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that α7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.

The appetitively motivated "cognitive" holeboard: a family of complex spatial discrimination tasks for assessing learning and memory.

Spatial learning and memory tasks have captured a solid position in neuroscience research. A variety of holeboard-type tasks are suitable for investigating the effects of a broad range of experimental manipulations on spatial learning and memory in a broad range of species, including fish, rodents, cats, pigs, tupaias, and humans. We summarize the concepts and procedures underlying tests of spatial discrimination learning, with special emphasis on holeboard-type tasks and task-specific characteristics. Holeboard-type tasks enable a broad range of mnemonic and cognitive variables to be measured in parallel, including cognitive processes such as habituation processes, spatial working and reference memory, and search strategies, but also non-cognitive variables, such as exploration, anxiety-related behavior, and stereotypies. These tasks are sensitive to a large number of naturally occurring differences (e.g. strain differences and age effects) and to the effects of non-genetic (e.g. specific brain lesions, stress, treatment with cognition impairers or cognition enhancers) and genetic experimental manipulations. In conclusion, holeboard-type tasks provide powerful tools to investigate multiple aspects of spatial orientation behavior in the same experimental setup. Cross-species comparison of holeboard performance shows the potential for translational studies.

The pig as a model animal for studying cognition and neurobehavioral disorders.

In experimental animal research, a short phylogenetic distance, i.e., high resemblance between the model species and the species to be modeled is expected to increase the relevance and generalizability of results obtained in the model species. The (mini)pig shows multiple advantageous characteristics that have led to an increase in the use of this species in studies modeling human medical issues, including neurobehavioral (dys)functions. For example, the cerebral cortex of pigs, unlike that of mice or rats, has cerebral convolutions (gyri and sulci) similar to the human neocortex. We expect that appropriately chosen pig models will yield results of high translational value. However, this claim still needs to be substantiated by research, and the area of pig research is still in its infancy. This chapter provides an overview of the pig as a model species for studying cognitive dysfunctions and neurobehavioral disorders and their treatment, along with a discussion of the pros and cons of various tests, as an aid to researchers considering the use of pigs as model animal species in biomedical research.