Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring.

Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.

Behavioral models in psychopathology: epistemic and semantic considerations.

The use of animals in neurosciences has a long history. It is considered indispensable in areas in which "translational" research is deemed invaluable, such as behavioral pharmacology and comparative psychology. Animal models are being used in pharmacology and genetics to screen for treatment targets, and in the field of experimental psychopathology to understand the neurobehavioral underpinnings of a disorder and of its putative treatment. The centrality of behavioral models betrays the complexity of the epistemic and semantic considerations which are needed to understand what a model is. In this review, such considerations are made, and the breadth of model building and evaluation approaches is extended to include theoretical considerations on the etiology of mental disorders. This expansion is expected to help improve the validity of behavioral models and to increase their translational value. Moreover, the role of theory in improving construct validity creates the need for behavioral scientists to fully engage this process.

Discrimination learning and judgment bias in low birth weight pigs.

Low birth weight (LBW) is a risk factor for cognitive and emotional impairments in humans. In pigs, LBW is a common occurrence, but its effects on cognition and emotion have received only limited scientific attention. To assess whether LBW pigs suffer from impaired cognitive and emotional development, we trained and tested 21 LBW and 21 normal birth weight (NBW) pigs in a judgment bias task. Judgment bias is a measure of emotional state which reflects the influence of emotion on an animal's interpretation of ambiguous stimuli. Pigs were trained to perform a specific behavioral response to two auditory stimuli, predicting either a positive or negative outcome. Once pigs successfully discriminated between these stimuli, they were presented with intermediate, ambiguous stimuli. The pigs' responses to ambiguous stimuli were scored as optimistic (performance of 'positive' response) or pessimistic (performance of 'negative' response). Optimistic or pessimistic interpretation of an ambiguous stimulus is indicative of a positive or negative emotional state, respectively. We found LBW pigs to require more discrimination training sessions than NBW pigs to reach criterion performance, suggesting that LBW causes a mild cognitive impairment in pigs. No effects of LBW on judgment bias were found, suggesting a similar emotional state for LBW and NBW pigs. This was supported by comparable salivary and hair cortisol concentrations for both groups. It is possible the enriched housing conditions and social grouping applied during our study influenced these results.

Decision-making under risk and ambiguity in low-birth-weight pigs.

Low birth weight (LBW) in humans is a risk factor for later cognitive, behavioural and emotional problems. In pigs, LBW is associated with higher mortality, but little is known about consequences for surviving piglets. Alteration in hypothalamic-pituitary-adrenal axis function in LBW pigs suggests altered emotionality, but no behavioural indicators have been studied. Decision-making under uncertain conditions, e.g., risk or ambiguity, is susceptible to emotional influences and may provide a means of assessing long-term effects of LBW in piglets. We tested LBW (N = 8) and normal-birth-weight (NBW; N = 8) male pigs in two decision-making tasks. For decision-making under risk, we developed a simple two-choice probabilistic task, the Pig Gambling Task (PGT), where an 'advantageous' option offered small but frequent rewards and a 'disadvantageous' option offered large but infrequent rewards. The advantageous option offered greater overall gain. For decision-making under ambiguity, we used a Judgement Bias Task (JBT) where pigs were trained to make an active response to 'positive' and 'negative' tone cues (signalling large and small rewards, respectively). Responses to ambiguous tone cues were rated as more or less optimistic. LBW pigs chose the advantageous option more often in later blocks of the PGT, and were scored as less optimistic in the JBT, than NBW pigs. Our findings demonstrate that LBW pigs have developed different behavioural strategies with respect to decision-making. We propose that this is guided by changes in emotionality in LBW piglets, and we provide behavioural evidence of increased negative affect in LBW piglets.

Pressure mat analysis of the longitudinal development of pig locomotion in growing pigs after weaning.

BACKGROUND: Gait evaluation is difficult in pigs, especially when objective and quantitative data are needed, thus little research has been conducted in this species. There is considerable experience, however, with objective gait analysis in other species, such as horses and dogs. In this study, a pressure mat was used to establish baseline kinetic data for gait and its longitudinal development in growing, weaned piglets.Ten clinically healthy weaned piglets were trained to trot over a pressure mat. Measurements were performed weekly during 10 weeks, starting at 5 weeks of age. Four kinetic parameters were recorded for all four limbs: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Three representative runs per measuring session per pig were collected. For each of the variables, left vs. right limb asymmetry-indices (ASI's) were calculated based on the average for that parameter per week. A linear mixed model was used to determine the influence of time (week), velocity, and limb (left vs. right, and fore vs. hind). Intra-class correlations were calculated to assess within-session replicability. RESULTS: Intra-class correlations showed good within-session replicability. Body-weight normalized PVF (nPVF), LR (nLR), VI (nVI) and PVP (nPVP) were higher in the forelimbs than in the hind limbs. A higher velocity was associated with a higher nPVF, nLR and nPVP. All parameters varied between weeks. ASI of LR and VI were higher in the forelimbs than in the hind limbs. Velocity and time did not influence ASI of any of the variables. CONCLUSIONS: Kinetic pressure mat measurements from healthy weaned piglets are highly replicable within-session. However, these variables present a significant variability between-session, which may be due to conformational changes of the young, growing piglets. Velocity clearly influences nPVF, nLR and nPVP, and all kinetic variables have higher values in forelimbs than in hind limbs. As time and velocity do not affect ASI's, the latter are preferable tools when velocity cannot be controlled or when measurements are repeated over longer time intervals. The present study supports the use of a pressure mat as an objective way to analyze and quantify porcine gait.

Pressure mat analysis of naturally occurring lameness in young pigs after weaning.

BACKGROUND: Lameness is a common problem in modern swine husbandry. It causes welfare problems in affected pigs as well as financial problems for farmers. To minimize these negative consequences of lameness, new treatment and prevention strategies need to be developed and validated using objective and quantitative measurement techniques. An example of such a putative diagnostic tool is the use of a pressure mat. Pressure mats are able to provide both objective loading (kinetic) as well as objective movement (kinematic) information on pig locomotion.In this study, pressure mat analysis was used to assess compensatory force redistribution in lame pigs; in particular a predefined set of four pressure mat parameters was evaluated for its use to objectively distinguish clinically lame from sound pigs. Kinetic data from 10 clinically lame and 10 healthy weaned piglets were collected. These data were analyzed to answer three research questions. Firstly the pattern of compensatory weight distribution in lame animals was studied using the asymmetry indices (ASI) for several combinations of limbs. Secondly, the correlation between total left-right asymmetry index and visual scores of lameness was assessed. Thirdly, by using receiver-operated curve (ROC) analysis, optimal cutoff values for these ASIs were then calculated to objectively detect lame pigs. RESULTS: Lame animals generally showed a shift in loading towards their diagonal and contralateral limbs, resulting in a clear left-right asymmetry. The degree of lameness as graded by visual scoring correlated well with the total left-right ASIs. Lame pigs could be objectively distinguished from sound pigs based on clear cutoff points calculated by ROC analysis for the complete set of four evaluated parameters. CONCLUSIONS: The gait of lame pigs is asymmetric, due to the unloading of the affected limb and concomitant weight redistribution towards other limbs. This asymmetry objectively expressed as total left-right asymmetry, correlates well with the subjective visual lameness scoring and can be used to objectively distinguish lame from sound pigs. Pressure mat gait analysis of pigs, therefore, appears to be a promising and useful tool to objectively quantify and possibly early detect lameness in pigs.

Performance of conventional pigs and Göttingen miniature pigs in a spatial holeboard task: effects of the putative muscarinic cognition impairer Biperiden.

BACKGROUND: The pig is emerging as a model species that bridges the gap between rodents and humans in research. In particular, the miniature pig (referred to hereafter as the minipig) is increasingly being used as non-rodent species in pharmacological and toxicological studies. However, there is as yet a lack of validated behavioral tests for pigs, although there is evidence that the spatial holeboard task can be used to assess the working and reference memory of pigs. In the present study, we compared the learning performance of commercial pigs and Göttingen minipigs in a holeboard task. METHODS: Biperiden, a muscarinic M1 receptor blocker, is used to induce impairments in cognitive function in animal research. The two groups of pigs were treated orally with increasing doses of biperiden (0.05 - 20 mg.kg-1) after they had reached asymptotic performance in the holeboard task. RESULTS: Both the conventional pigs and the Göttingen minipigs learned the holeboard task, reaching nearly errorless asymptotic working and reference memory performance within approximately 100 acquisition trials. Biperiden treatment affected reference, but not working, memory, increasing trial duration and the latency to first hole visit at doses ≥ 5 mg.kg-1. CONCLUSION: Both pig breeds learned the holeboard task and had a comparable performance. Biperiden had only a minor effect on holeboard performance overall, and mainly on reference memory performance. The effectiveness needs to be evaluated further before definitive conclusions can be drawn about the ability of this potential cognition impairer in pigs.

Successive and conditional discrimination learning in pigs.

We studied the ability of pigs to discriminate tone cues using successive and conditional discrimination tasks. Pigs (n = 8) were trained in a successive discrimination Go/No-Go task (Experiment 1) to associate a Go-cue with a reward at the end of a runway and a No-Go-cue with the absence of reward. Latency to reach the goal-box was recorded for each cue-type. Learning of a conditional discrimination task was compared between low-birthweight (LBW, n = 5) and normal-birthweight (NBW, n = 6) pigs (Experiment 2) and between conventional farm (n = 7) and Göttingen miniature (n = 8) pigs (Experiment 3). In this active-choice task, one cue signalled a response in a right goal-box was correct and a second cue signalled a response in a left goal-box was correct. Cues were differentially rewarded. The number of sessions to learn the discrimination and number of correct choices per cue-type were recorded. In Experiment 1, four out of eight pigs showed learning on the task, that is, a higher latency to respond to the No-Go-cue, within 25 sessions. In Experiment 2, eight out of 11 pigs learned the discrimination within 46 sessions. LBW learners learned faster than NBW learners. In Experiment 3, all 15 pigs learned the task within 16 sessions. Göttingen miniature pigs learned faster than conventional farm pigs. While some methodological issues may improve the Go/No-Go design, it is suggested that an active-choice task yields clearer and more consistent results than one relying on latency alone.

Assessing learning and memory in pigs.

In recent years, there has been a surge of interest in (mini) pigs (Sus scrofa) as species for cognitive research. A major reason for this is their physiological and anatomical similarity with humans. For example, pigs possess a well-developed, large brain. Assessment of the learning and memory functions of pigs is not only relevant to human research but also to animal welfare, given the nature of current farming practices and the demands they make on animal health and behavior. In this article, we review studies of pig cognition, focusing on the underlying processes and mechanisms, with a view to identifying. Our goal is to aid the selection of appropriate cognitive tasks for research into pig cognition. To this end, we formulated several basic criteria for pig cognition tests and then applied these criteria and knowledge about pig-specific sensorimotor abilities and behavior to evaluate the merits, drawbacks, and limitations of the different types of tests used to date. While behavioral studies using (mini) pigs have shown that this species can perform learning and memory tasks, and much has been learned about pig cognition, results have not been replicated or proven replicable because of the lack of validated, translational behavioral paradigms that are specially suited to tap specific aspects of pig cognition. We identified several promising types of tasks for use in studies of pig cognition, such as versatile spatial free-choice type tasks that allow the simultaneous measurement of several behavioral domains. The use of appropriate tasks will facilitate the collection of reliable and valid data on pig cognition.

Physiological and behavioral reactions elicited by simulated and real-life visual and acoustic helicopter stimuli in dairy goats.

BACKGROUND: Anecdotal reports and a few scientific publications suggest that flyovers of helicopters at low altitude may elicit fear- or anxiety-related behavioral reactions in grazing feral and farm animals. We investigated the behavioral and physiological stress reactions of five individually housed dairy goats to different acoustic and visual stimuli from helicopters and to combinations of these stimuli under controlled environmental (indoor) conditions. The visual stimuli were helicopter animations projected on a large screen in front of the enclosures of the goats. Acoustic and visual stimuli of a tractor were also presented. On the final day of the study the goats were exposed to two flyovers (altitude 50 m and 75 m) of a Chinook helicopter while grazing in a pasture. Salivary cortisol, behavior, and heart rate of the goats were registered before, during and after stimulus presentations. RESULTS: The goats reacted alert to the visual and/or acoustic stimuli that were presented in their room. They raised their heads and turned their ears forward in the direction of the stimuli. There was no statistically reliable rise of the average velocity of moving of the goats in their enclosure and no increase of the duration of moving during presentation of the stimuli. Also there was no increase in heart rate or salivary cortisol concentration during the indoor test sessions. Surprisingly, no physiological and behavioral stress responses were observed during the flyover of a Chinook at 50 m, which produced a peak noise of 110 dB. CONCLUSIONS: We conclude that the behavior and physiology of goats are unaffected by brief episodes of intense, adverse visual and acoustic stimulation such as the sight and noise of overflying helicopters. The absence of a physiological stress response and of elevated emotional reactivity of goats subjected to helicopter stimuli is discussed in relation to the design and testing schedule of this study.

The Relation between Hair-Cortisol Concentration and Various Welfare Assessments of Dutch Dairy Farms.

Many protocols have been developed to assess farm animal welfare. However, the validity of these protocols is still subject to debate. The present study aimed to compare nine welfare assessment protocols, namely: (1) Welfare Quality© (WQ), (2) a modified version of Welfare Quality (WQ Mod), which has a better discriminative power, (3) WelzijnsWijzer (Welfare Indicator; WW), (4) a new Welfare Monitor (WM), (5) Continue Welzijns Monitor (Continuous Welfare Monitor; CWM), (6) KoeKompas (Cow Compass; KK), (7) Cow Comfort Scoring System (CCSS), (8) Stall Standing Index (SSI) and (9) a Welfare Index (WI Tuyttens). In addition, a simple welfare estimation by veterinarians (Estimate vets, EV) was added. Rank correlation coefficients were calculated between each of the welfare assessment protocol scores and mean hair cortisol concentrations from 10 cows at 58 dairy farms spread over the Netherlands. Because it has been suggested that the hair cortisol level is related to stress, experienced over a long period of time, we expected a negative correlation between cortisol and the result of the welfare protocol scores. Only the simple welfare estimation by veterinarians (EV) (ρ = -0.28) had a poor, but significant, negative correlation with hair cortisol. This correlations, however, failed to reach significance after correction of p-values for multiple correlations. Most of the results of the different welfare assessment protocols had a poor, fair or strong positive correlation with each other, supporting the notion that they measure something similar. Additional analyses revealed that the modified Welfare Quality protocol parameters housing (ρ = -0.30), the new Welfare Monitor (WM) parameter health (ρ = -0.33), and milk yield (ρ = -0.33) showed negative correlations with cortisol. We conclude that because only five out of all the parameter scores from the welfare assessment protocols showed a negative, albeit weak, correlation with cortisol, hair cortisol levels may not provide a long term indicator for stress in dairy cattle, or alternatively, that the protocols might not yield valid indices for cow welfare.

Spatial memory deficits after vincristine-induced lesions to the dorsal hippocampus.

Vincristine is a commonly used cytostatic drug for the treatment of leukemia, neuroblastoma and lung cancer, which is known to have neurotoxic properties. The aim of this study was to assess the effects of vincristine, injected directly into the dorsal hippocampus, in spatial memory using the spatial cone field discrimination task. Long Evans rats were trained in the cone field, and after reaching training criterion received bilateral vincristine infusions into the dorsal hippocampus. Vincristine-treated animals presented unilateral or bilateral hippocampal lesions. Animals with bilateral lesions showed lower spatial working and reference memory performance than control animals, but task motivation was unaffected by the lesions. Working and reference memory of animals with unilateral lesions did not differ from animals with bilateral lesions and control animals. In sum, intrahippocampal injection of vincristine caused profound tissue damage in the dorsal hippocampus, associated with substantial cognitive deficits.

A Monosodium Iodoacetate Osteoarthritis Lameness Model in Growing Pigs.

Lameness is a common problem in pigs, causing welfare issues in affected pigs and economic losses for farmers. It is often caused by osteoarthrosis (OA) in its acute or chronic form. We assessed face and construct validity of a potential model for naturally-occurring OA and its progression to chronic OA. Such a model would allow the assessment of possible interventions. Monosodium-iodoacetate (MIA) or isotonic saline was deposited in the intercarpal joint of 20 growing pigs. Functional effects were assessed using subjective (visual lameness scoring) and objective (kinetic gait analysis) techniques at several timepoints. Structural effects were assessed by histopathology at 68 days. Eight out of 10 MIA treated animals had histopathological OA lesions confirmed in the target joint, while for all saline treated animals the target joint was judged to be normal. Pressure mat analysis revealed increased asymmetric weight bearing in these animals compared to the control group on day 3, 14, 28 and 56. Visual scoring only showed a difference between groups on day 1. MIA did not cause prolonged visible lameness, thus face validity for OA under field conditions was not entirely met. Since objective gait parameters showed decreased weightbearing as a behavioral expression of pain, it may be used as a general model for movement-induced pain in pigs.

Effects of parity and litter size on cortisol measures in commercially housed sows and their offspring.

Breeding sows are regularly exposed to on-farm stressors throughout the duration of their production period. The impact of such stressors may differ for primi- and multiparous sows, as sows could learn to cope with stressors as they gain experience with them. If parity affects stress in sows, it may also impact their prenatal offspring through differential maternal stress. In addition to parity, litter size is another potential factor involved in stress of sows and piglets. Larger litters may be a source of discomfort for gestating sows, while it can result in intra-uterine growth restriction of piglets. In the current study, we aimed to assess whether parity and litter size affect cortisol measures in breeding sows and their offspring. To do this, we measured salivary cortisol concentrations of 16 primiparous and 16 multiparous sows at three time points: 1) while sows were group housed, 2) after sows were separated from the group prior to moving to the farrowing unit and 3) after handling procedures. In addition, hair cortisol concentration was determined for the sows during late gestation and for their low birth weight (n = 63) and normal birth weight (n = 43) offspring on day 3 after birth, to reflect in-utero cortisol exposure. It was expected that if sows adapt to on-farm stressors, the more experienced, multiparous sows would show decreased stress responses in comparison to primiparous sows. However, we found a comparable acute stress response of primi- and multiparous sows to separation from the group. Handling procedures did not influence sows' salivary cortisol concentrations. Sows' hair cortisol concentration was positively correlated with litter size. Future research is needed to assess whether this finding reflects increased stress in sows carrying larger litters. Parity or litter size did not have a direct effect on their offspring's hair cortisol concentration. Larger litters did have a higher occurrence of low birth weight piglets. For these piglets, females had higher neonatal hair cortisol concentrations than males. Overall, our results indicate that breeding sows do not adapt to all on-farm stressors. In addition, litter size may influence HPA axis activity in both sows and piglets.

Early-postnatal iron deficiency impacts plasticity in the dorsal and ventral hippocampus in piglets.

In this study, we investigated whether alterations in plasticity markers such as brain-derived neurotrophic factor (BDNF), p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB) are underlying iron deficiency (ID)-induced cognitive impairments in iron depleted piglets. Newborn piglets were either fed an iron-depleted diet (21mg Fe/kg) or an iron-sufficient diet (88mg Fe/kg) for four weeks. Subsequently, eight weeks after iron repletion (190-240mg Fe/kg) we found a significant decrease in mature BDNF (14kDa) and proBDNF (18kDa and 24kDa) protein levels in the ventral hippocampus, whereas we found increases in the dorsal hippocampus. The phosphorylation of cAMP response element binding protein (CREB) follows the mature BDNF protein level pattern. No effects were found on BDNF and CREB protein levels in the prefrontal cortex. The protein levels of the high affinity BDNF receptor, TrkB, was significantly decreased in both dorsal and ventral hippocampus of ID piglets, whereas it was increased in the prefrontal cortex. Together, our data suggest a disrupted hippocampal plasticity upon postnatal ID.

Mutilating Procedures, Management Practices, and Housing Conditions That May Affect the Welfare of Farm Animals: Implications for Welfare Research.

A number of mutilating procedures, such as dehorning in cattle and goats and beak trimming in laying hens, are common in farm animal husbandry systems in an attempt to prevent or solve problems, such as injuries from horns or feather pecking. These procedures and other practices, such as early maternal separation, overcrowding, and barren housing conditions, raise concerns about animal welfare. Efforts to ensure or improve animal welfare involve adapting the animal to its environment, i.e., by selective breeding (e.g., by selecting "robust" animals) adapting the environment to the animal (e.g., by developing social housing systems in which aggressive encounters are reduced to a minimum), or both. We propose adapting the environment to the animals by improving management practices and housing conditions, and by abandoning mutilating procedures. This approach requires the active involvement of all stakeholders: veterinarians and animal scientists, the industrial farming sector, the food processing and supply chain, and consumers of animal-derived products. Although scientific evidence about the welfare effects of current practices in farming such as mutilating procedures, management practices, and housing conditions is steadily growing, the gain in knowledge needs a boost through more scientific research. Considering the huge number of animals whose welfare is affected, all possible effort must be made to improve their welfare as quickly as possible in order to ban welfare-compromising procedures and practices as soon as possible.

Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs.

Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long-term use of meloxicam in young, growing piglets.

Making Decisions under Ambiguity: Judgment Bias Tasks for Assessing Emotional State in Animals.

Judgment bias tasks (JBTs) are considered as a family of promising tools in the assessment of emotional states of animals. JBTs provide a cognitive measure of optimism and/or pessimism by recording behavioral responses to ambiguous stimuli. For instance, a negative emotional state is expected to produce a negative or pessimistic judgment of an ambiguous stimulus, whereas a positive emotional state produces a positive or optimistic judgment of the same ambiguous stimulus. Measuring an animal's emotional state or mood is relevant in both animal welfare research and biomedical research. This is reflected in the increasing use of JBTs in both research areas. We discuss the different implementations of JBTs with animals, with a focus on their potential as an accurate measure of emotional state. JBTs have been successfully applied to a very broad range of species, using many different types of testing equipment and experimental protocols. However, further validation of this test is deemed necessary. For example, the often extensive training period required for successful judgment bias testing remains a possible factor confounding results. Also, the issue of ambiguous stimuli losing their ambiguity with repeated testing requires additional attention. Possible improvements are suggested to further develop the JBTs in both animal welfare and biomedical research.

Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation.

RATIONALE: Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes. OBJECTIVE: We investigated the memory-enhancing effects of the PDE5 inhibitor sildenafil and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. METHODS: The object recognition task measures whether rats remembered an object they have explored in a previous learning trial. All drugs were given orally 30 min before or immediately after learning to study acquisition and consolidation, respectively. RESULTS: Sildenafil given immediately after the first trial improved the memory performance after 24 h and resulted in an inverted U-shaped dose-effect curve with the peak dose at 3 mg/kg. When given before the first trial, sildenafil also improved the memory performance. However, the dose needed for the best performance under this condition was 10 mg/kg, suggesting that the dose-effect curve shifted to the right. This can be explained by the metabolic clearance of the high dose of sildenafil. Donepezil had no memory improving effect when given after the first trial. However, when given before the first trial, a gradually increasing dose-effect curve was found which had its maximum effect at the highest dose tested (1 mg/kg). Likewise, only when metrifonate (30 mg/kg) was given before the first trial did rats show an improved memory performance. CONCLUSION: Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information.

Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P <0.001). It was concluded that measurement of gait asymmetry by pressure mat analysis and locomotor activity in an open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs.