Implementation of automated cognitive testing systems for socially housed rhesus (Macaca mulatta) and squirrel (Saimiri spp.) monkeys: Age differences in learning.

Utilizing Automated Cognitive Testing Systems (ACTS) with group-housed nonhuman primates offers a number of advantages over manual testing and computerized testing of singly housed subjects. To date, ACTS usage has been limited to great apes or African monkeys. Here, we detail what we have learned while implementing ACTS with socially housed squirrel monkeys and rhesus macaques and provide information about the training process.

Behavioral and Cognitive Outcomes of Rhesus Macaques Following Neonatal Exposure to Antiseizure Medications.

Objective: Exposure of neonatal macaques to the antiseizure medications phenobarbital and midazolam (PbM) causes widespread apoptotic death of neurons and oligodendrocytes. We studied behavior and neurocognitive performance in 12 to 24 month-old macaques treated as neonates with PbM.

Methods: A total of 14 monkeys received phenobarbital and midazolam over 24 hours under normothermia (n = 8) or mild hypothermia (n = 6).

Improving transparency-A call to include social housing information in biomedical research articles involving nonhuman primates.

The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility.

Predicting their past: Machine language learning can discriminate the brains of chimpanzees with different early-life social rearing experiences.

Early life experiences, including separation from caregivers, can result in substantial, persistent effects on neural, behavioral, and physiological systems as is evidenced in a long-standing literature and consistent findings across species, populations, and experimental models. In humans and other animals, differential rearing conditions can affect brain structure and function. We tested for whole brain patterns of morphological difference between 108 chimpanzees reared typically with their mothers (MR; N = 54) and those reared decades ago in a nursery with peers, human caregivers, and environmental enrichment (NR; N = 54).

Moving evidence into practice: cost analysis and assessment of macaques' sustained behavioral engagement with videogames and foraging devices.

Environmental enrichment plans for captive nonhuman primates often include provision of foraging devices. The rationale for using foraging devices is to promote species-typical activity patterns that encourage physical engagement and provide multi-sensory stimulation. However, these devices have been shown to be ineffective at sustaining manipulation over long periods of time, and often produce minimal cognitive engagement.

Assessment of foraging devices as a model for decision-making in nonhuman primate environmental enrichment.

Continued progress to move evidence-based best practices into community and regulatory animal welfare standards depends in part on developing common metrics to assess cost, benefit, and relative value. Here we describe a model approach to evidence-based evaluation and an example of comprehensive cost-benefit assessment for a common element of environmental enrichment plans for laboratory-housed nonhuman primates. Foraging devices encourage a species-typical activity that dominates the time budget of primates outside captivity and provide inherent cognitive challenges, physical activity demands, and multi-sensory stimulation.

Assessing anxiety in nonhuman primates.

Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments.

Evolution of the central sulcus morphology in primates.

The central sulcus (CS) divides the pre- and postcentral gyri along the dorsal-ventral plane of which all motor and sensory functions are topographically organized. The motor-hand area of the precentral gyrus or KNOB has been described as the anatomical substrate of the hand in humans. Given the importance of the hand in primate evolution, here we examine the evolution of the motor-hand area by comparing the relative size and pattern of cortical folding of the CS surface area from magnetic resonance images in 131 primates, including Old World monkeys, apes and humans.

The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells.

Early-life adversity is associated with a broad scope of life-long health and behavioral disorders. Particularly critical is the role of the mother. A possible mechanism is that these effects are mediated by "epigenetic" mechanisms.

Chronic treatment with extended release methylphenidate does not alter dopamine systems or increase vulnerability for cocaine self-administration: a study in nonhuman primates.

Despite the widespread use of stimulant medications for the treatment of attention deficit hyperactivity disorder, few studies have addressed their long-term effects on the developing brain or susceptibility to drug use in adolescence. Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N=8 per group).

Cortical sulci asymmetries in chimpanzees and macaques: a new look at an old idea.

Functional and neuroanatomical asymmetries are an important characteristic of the human brain. The evolution of such specializations in the human cortex has provoked great interest in primate brain evolution. Most research on cortical sulci has revolved around linear measurements, which represent only one dimension of sulci organization.

The influences of perinatal challenge persist into the adolescent period in socially housed bonnet macaques (Macaca radiata).

Social challenges during the perinatal period influence the mother-infant relationship in nonhuman primates and may affect the offspring's response to later social challenge(s). Relocation of a breeding colony of monkeys (Macaca radiata) created two groups of infants: one group experienced social group relocation to a new housing facility during the perinatal period (ATYPICAL) and the second group developed within a constant environment (TYPICAL). At a mean age of 25 months, all animals were removed from their natal group and placed in same sex adolescent social groups.

Aging and physical mobility in group-housed Old World monkeys.

While indices of physical mobility such as gait speed are significant predictors of future morbidity/mortality in the elderly, mechanisms of these relationships are not understood. Relevant animal models of aging and physical mobility are needed to study these relationships. The goal of this study was to develop measures of physical mobility including activity levels and gait speed in Old World monkeys which vary with age in adults.

Long-term effects of differential early rearing in rhesus macaques: behavioral reactivity in adulthood.

Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP).

Planum temporale grey matter asymmetries in chimpanzees (Pan troglodytes), vervet (Chlorocebus aethiops sabaeus), rhesus (Macaca mulatta) and bonnet (Macaca radiata) monkeys.

Brain asymmetries, particularly asymmetries within regions associated with language, have been suggested as a key difference between humans and our nearest ancestors. These regions include the planum temporale (PT) - the bank of tissue that lies posterior to Heschl's gyrus and encompasses Wernicke's area, an important brain region involved in language and speech in the human brain. In the human brain, both the surface area and the grey matter volume of the PT are larger in the left compared to right hemisphere, particularly among right-handed individuals.

Hematological and serum biochemical indices in healthy bonnet macaques (Macaca radiata).

Background: Blood reference values for bonnet macaques (Macaca radiata) are limited. The goal of this study was to determine reference ranges for hematological and serum biochemical indices in healthy, socially housed bonnet macaques for males and females over a range of ages.

Methods: Blood hematological and serum biochemical values were obtained from 50 healthy bonnet macaques of both sexes and aged 10-234 months.

Multidimensional cost-benefit analysis to guide evidence-based environmental enrichment: providing bedding and foraging substrate to pen-housed monkeys.

Refinement of animal care and housing is an important shared goal-and challenge-of the team of research, veterinary, and animal care personnel charged with ensuring the wellbeing of laboratory animals. This study addresses 2 issues central to decision-making and implementation of environmental enhancement: methods for useful and comprehensive cost analysis and evaluation of engineering, husbandry, and facilities considerations. The study was undertaken to analyze the feasibility and cost of providing wood shavings as a floor cover for pen-housed monkeys.

Age-related neuroanatomical differences from the juvenile period to adulthood in mother-reared macaques (Macaca radiata).

Basic data on age-related neuroanatomical changes across the juvenile to adult period in nonhuman primates is sparse, and this gap in knowledge is a serious impediment to translational research aimed at understanding brain development across the lifespan. In this study, magnetic resonance images were analyzed for fifteen mother-reared, socially-housed bonnet macaques (Macaca radiata) in three age groups: juvenile, adolescent, and adult. These data are the first to show age-related changes in gray:white matter ratio and corpus callosum size in bonnet macaques.

Behavioral and neuroanatomical correlates of white matter asymmetries in chimpanzees (Pan troglodytes).

Although behavioral and brain asymmetries have been documented in non-human primates, lateralization in cortical connectivity as reflected in white matter has not been described in any species, despite the intrinsic theoretical interest in white matter expansion during primate brain evolution. Here we report evidence of population-level leftward asymmetries in the white matter of chimpanzees. We further report that lateralization in white matter correlates with their handedness as well as neuroanatomical asymmetries in the precentral gyrus.

Apo-AII is an elevated biomarker of chronic non-human primate ethanol self-administration.

Aims: Serum protein profiles were examined in naïve, ethanol self-administering and ethanol abstinent cynomolgus monkeys (Macaca fasicularis) to search for differences in protein expression which could possibly serve as biomarkers of heavy ethanol consumption.

Methods: Surface-enhanced laser desorption ionization time-of-flight (SELDI-ToF) mass spectrometry was used for proteomic profiling of serum.

Results: Two proteins were identified by SELDI-ToF to be increased in ethanol self-administering compared with abstinent animals.

Long-term ethanol self-administration by cynomolgus macaques alters the pharmacology and expression of GABAA receptors in basolateral amygdala.

We have recently demonstrated that chronic ethanol ingestion alters the functional and pharmacological properties of GABAA receptors measured in acutely isolated rat lateral/basolateral amygdala neurons, a limbic forebrain region involved with fear-learning and innate anxiety. To understand relevance of these results in the context of primates, we have examined the effects of long-term ethanol self-administration on basolateral amygdala GABAA receptor pharmacology and expression in cynomolgus macaques (Macaca fascicularis). The impact of this 18-month-long exposure on GABAA receptor function was assessed in acutely isolated neurons from basolateral amygdala with whole-cell patch-clamp electrophysiology.

Building bridges: the transdisciplinary study of craving from the animal laboratory to the lamppost.

This article represents the proceedings of a symposium at the 2003 Research Society on Alcoholism meeting in Ft. Lauderdale, Florida, organized and chaired by Peter M. Monti.

The future of proteomics in the study of alcoholism.

This article represents the proceedings of a workshop at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The workshop organizers/chairpersons were Chinnaswamy Kasinathan and Paul Manowitz. The presentations were (1) Introduction to the field of proteomics, by Kent Vrana; (2) Use of proteomics in the identification of urinary biomarkers for alcohol intake, by Chinnaswamy Kasinathan, Paul Thomas, and Paul Manowitz; (3) Proteomics screening illuminates ethanol-mediated induction of HDL proteins in macaques, by Kent Vrana, Randy Gooch, Travis Worst, Stephen Walker, Aaron Xu, Peter Pierre, Heather Green, and Kathleen Grant; and (4) Proteomics applied to the study of the liver, by Laura Beretta.