The impulsive horse: Comparing genetic, physiological and behavioral indicators to those of human addiction.

Stress and genotype elicit changes in impulse control in a range of species that are attributable to adaptations in both the central and peripheral nervous system. We examined aspects of this mechanism in the horse by assessing the effect of a dopamine receptor genotype (DRD4) and central dopaminergic tone (measured via spontaneous blink rate [SBR] and behavioral initiation rate [BIR]), on measures of impulsivity, compulsivity (3-choice serial reaction time task) and sympathetic/ parasympathetic system balance (heart rate variability [HRV]). Genotype did not have a significant effect on any of the parameters measured. SBR but not BIR correlated significantly with levels of impulsivity. There was no clear association of HRV parameters with either measures of central dopaminergic activity or impulsivity/compulsivity. Overall, some elements of the data suggest that the horse may be a useful animal model for assessing the genetic and environmental factors that lead to the physiological and behavioral phenotype of human addiction, particularly when considering the relationship between central dopaminergic tone and impulsivity.

Assessing the Value of the Zebrafish Conditioned Place Preference Model for Predicting Human Abuse Potential.

Regulatory agencies recommend that centrally active drugs are tested for abuse potential before approval. Standard preclinical assessments are conducted in rats or non-human primates (NHPs). This study evaluated the ability of the zebrafish conditioned place preference (CPP) model to predict human abuse outcomes. Twenty-seven compounds from a variety of pharmacological classes were tested in zebrafish CPP, categorized as positive or negative, and analyzed using standard diagnostic tests of binary classification to determine the likelihood that zebrafish correctly predict robust positive signals in human subjective effects studies (+HSE) and/or Drug Enforcement Administration drug scheduling. Results were then compared with those generated for rat self-administration and CPP, as well as NHP self-administration, using this same set of compounds. The findings reveal that zebrafish concordance and sensitivity values were not significantly different from chance for both +HSE and scheduling. Although significant improvements in specificity and negative predictive values were observed for zebrafish relative to +HSE, specificity without sensitivity provides limited predictive value. Moreover, assessments in zebrafish provided no added value for predicting scheduling. By contrast, rat and NHP models generally possessed significantly improved concordance, sensitivity, and positive predictive values for both clinical measures. Although there may be predictive value with compounds from specific pharmacological classes (e.g., µ-opioid receptor agonists, psychostimulants) for zebrafish CPP, altogether these data highlight that using the current methodology, the zebrafish CPP model does not add value to the preclinical assessment of abuse potential.

Molecular psychiatry of zebrafish.

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research.

Effect of low light and high noise on behavioural activity, physiological indicators of stress and production in laying hens.

1. Commercial laying hens are commonly housed in noisy and dim environments, yet relatively little is known about whether these conditions, particularly in combination, have any effect on welfare or egg production. 2. The study was designed to investigate whether chronic exposure to continuous noise (60 dB(A) vs. 80 dB(A)) and/or light intensity (150 lux vs. 5 lux) during the critical period of coming into lay (16-24 weeks of age) influenced behaviour (activity, resting and feather maintenance), physiological stress (plasma corticosterone and heterophil to lymphocyte ratio) and production (number and weight of eggs laid) in laying hens. 3. Hens in the low light pens were less active and preened and dust-bathed more than those housed in 150 lux; hens in the high noise pens rested more frequently than those in quieter pens. 4. There was no evidence that chronic exposure to low light or high noise caused appreciable physiological stress but egg production was affected by these conditions. Hens kept in pens with low light or high noise laid fewer eggs per day than those kept in high light or low noise pens. These effects were additive, so that the fewest eggs were laid by hens subject to both low light and high noise. 5. These results show that low light intensity and continual high background noise have a detrimental effect on egg production in the early laying phase as well as influencing the time allocated to different behaviours. However there was no strong evidence for a physiological stress response to either of these conditions or their combination.

The impact of chronic environmental stressors on growing pigs, Sus scrofa (Part 1): stress physiology, production and play behaviour.

Commercially farmed animals are frequently housed in conditions that impose a number of concurrent environmental stressors. For pigs housed indoors, elevated levels of mechanical noise, atmospheric ammonia and low light intensities are commonplace. This experiment examined the effects on growing pigs of chronic exposure to combinations of commercially relevant levels of these potential stressors. Four-week-old hybrid female pigs (n = 224) were housed under experimentally manipulated conditions of nominally either <5 or 20 ppm atmospheric concentration of ammonia (24 h), a light intensity of 40 lux or 200 lux (12 h) and mechanical noise at either ⩽60 or 80 dB(A) (24 h) for 15 weeks in a fully factorial arrangement (23) of treatments. The response of pigs to these environmental factors was assessed using a suite of physiological, production and behavioural measures. These included indicators of hypothalamic-pituitary-adrenal (HPA) axis activation such as salivary cortisol and adrenal morphometry, as well as body weight, food conversion efficiency and general health scores. Play behaviour was recorded as it is thought to be inversely related to stress. Chronic exposure to ammonia produced the strongest effect, shown by lower concentrations of salivary cortisol and larger adrenal cortices in the pigs reared under 20 ppm ammonia, which may have been indicative of a period of HPA activation leading to a downregulation of cortisol production. The pigs in the ammoniated rooms also performed less play behaviour than pigs in non-ammoniated rooms. There was evidence for an interaction between high noise and ammonia on the health scores of pigs and for brighter light to ameliorate the effect of ammonia on salivary cortisol. However, there was no measurable impact of these potential stressors on the productivity of the pigs or any of the other physiological parameters measured. We conclude that there should be little concern in terms of performance about the physical stressors tested here, within current European Union legal limits. However, 20 ppm ammonia may have had an adverse influence on the well-being of growing pigs. In this study, all other aspects of the pigs' husbandry were optimal; therefore, it is possible that under less favourable conditions, more pronounced effects of ammonia, noise and dim light would be observed.

The impact of chronic environmental stressors on growing pigs, Sus scrofa (Part 2): social behaviour.

The effects of common and concurrent environmental stressors on the social behaviour of farm animals are poorly understood. Here, we report the results of a multifactorial experiment designed specifically to examine the individual, additive or interactive effects of elevated ammonia, noise and low light (LL) levels on the social behaviour of growing pigs. Social behaviour was measured in terms of the nature, frequency and duration of both initiated and response behaviours for 4 weeks following mixing of the groups. General activity patterns, group cohesion and social discrimination were also examined as a function of the environmental treatments. Elevated concentrations of atmospheric ammonia (∼20 v. <5 ppm) and LL intensity (∼40 v. 200 lux) had the most pronounced effects, particularly on the nature of social interactions, with pigs under these conditions showing more aggression in the early stages of the experiment. In addition, pigs exposed to a high level of mechanical noise representative of artificial ventilation (∼80 v. 40 dB [A]) were less submissive to aggressive acts, while pigs in ∼20 ppm ammonia showed more reciprocated aggression when in coincident LL (<40 lux). The results indicate that atmospheric ammonia at commonly experienced concentrations may undermine social stability, particularly in the presence of low lighting, though the mechanisms are currently unknown. These findings have implications for the welfare of growing pigs and hence policy makers and farmers alike, with respect to the improvement of welfare in intensive pig farming.