E. A. M. Scott

A novel method for activity monitoring in small non-human primates

Patterns of spontaneous activity are valuable reflections of well-being in animals and humans and, because of this, investigations have frequently incorporated some form of activity monitoring into their studies. It is widely believed that activity monitoring, alongside assessments of general behaviour, should be included in initial CNS safety pharmacology screening. As the number of marmoset studies having actimetry as their focus, or as an adjunct, is increasing, we wished to evaluate an alternative approach to those commonly used. The method is based on miniaturized accelerometer technologies, currently used for human activity monitoring. Actiwatch®-Minis were used to monitor the activity of two groups of differently housed marmosets for 14 consecutive days. Group A consisted of four mixed-sex pairs of animals and group B comprised eight group-housed males. Activity profiles were generated for weekday and weekend periods. The devices captured quantifiable data which showed differences in total activity between the two differently housed groups and revealed intragroup variations in the temporal spread of activity between weekdays and weekends. The Actiwatch®-Mini has been shown to generate retrospective, data-logged activity counts recorded from multiple animals in a single arena by means of non-invasive monitoring.

Home cage presentation of complex discrimination tasks to marmosets and rhesus monkeys

The study reported here demonstrates the feasibility of presenting cognitive tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to either marmosets or rhesus monkeys in their home cages. This location of testing offers opportunities for the measurement of additional indices, for example spontaneous behaviour (Prowse et al. 1995) and electrophysiology (Pearce et al. 1998) as well as facilitating repeated test presentation. Results from 12 marmosets and 4 rhesus monkeys which have completed several sequences of an eight-stage discrimination task involving simple discriminations, compound discriminations and reversals are reported. The paradigm developed has application in long-term studies. Tests from CANTAB have been used extensively in normal humans (Robbins et al. 1994) as well as a range of patient groups (Owen et al. 1992, Elliott et al. 1995) and to assess drug effects (Coull et al. 1996). Additionally some of these tests have been presented to marmosets (Roberts et al. 1988) to examine neuropsychological functioning. This comparative approach facilitates meaningful cross species comparison, particularly in the study of the effects of pharmacological intervention.

Concurrent Monitoring of EEG and Performance in the Common Marmoset: A Methodological Approach

A model has been developed in a nonhuman primate, the common marmoset (Callithrix jacchus), which should enable the study of long term effects of compounds with potentially psychoactive properties. The technique facilitates concurrent monitoring of both behavioral and electrophysiological parameters while animals remain in their home cages. Subjects were trained to perform tests from a neuropsychological test battery (The Cambridge Neuropsychological Test Automated Battery, CANTAB) in which they learned to discriminate between pairs of stimuli presented on a touch sensitive computer screen. Single channel cortical electroencephalography (EEG) by radiotelemetry was simultaneously recorded while behavioral testing took place.

Investigation of the sleep electrocorticogram of the common marmoset (Callithrix jacchus) using radiotelemetry

OBJECTIVE To evaluate the use of a totally implantable radiotelemetry system for recording the sleep electrocorticogram (ECoG) of a small new world primate, the common marmoset (Callithrix jacchus) without restraint during data collection. METHODS Under anaesthesia a telemetry transmitter, which allowed the recording of a single ECoG channel, was implanted intraperitoneally. This system allowed ECoG data to be recorded overnight from animals living in pairs within their habitual laboratory environment over a period of 12 months. Data were subsequently scored using modified Rechtschaffen and Kales criteria (A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Los Angeles, UCLA Brain Information Service/Brain Research Institute, 1968) into stages of waking, light sleep, deep sleep and probable rapid eye movement sleep (pREM). Concurrent video recording was used to assist in the categorising of pREM. RESULTS Results showed that, as in man, the marmoset exhibits sleep cycles with stages alternating between non-REM (deep sleep and light sleep) and pREM sleep throughout the night. In common with other non-human primates the duration of each of the sleep stages was relatively short and punctuated with frequent waking. CONCLUSIONS These data suggest that sleep in marmosets housed under laboratory conditions (a) can be recorded without restraint and (b) has potential to be used as a model for human sleep.

The effects of acutely administered low dose sarin on cognitive behaviour and the electroencephalogram in the common marmoset

Previous studies have suggested that administration of a clinically sign-free dose of sarin to non-human primates gives rise to subtle changes in brain electrical activity as measured by electroencephalography (EEG) several months following exposure. The functional significances of such changes are unclear. The present study monitored EEG by using implantable radiotelemetry, and also assessed the performance of complex behavioural tasks, in non-human primates for up to 15 months following exposure to a low dose of sarin. Baselines of EEG and behaviour were shown to be stable over several months in control animals. The doses of sarin administered caused erythrocyte cholinesterase inhibitions of 36.4% to 67.1%. Overall, no significant changes in EEG patterns were observed although there were increases in beta 2 amplitude which approached significance (p=0.07). No deleterious effects on performance were seen on the touchscreen mediated discrimination tasks presented from the Cambridge Neuropsychological Test Automated Battery (CANTAB). This study illustrates the validity of the approach employed and makes an important contribution to the investigation of the long-term effects of organophosphorous compounds.

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets:

The long-term sequelae of exposure to low doses of organophosphate compounds are ill defined, with effects variously reported on a range of indices of central nervous system functions such as sleep, cognitive performance and electroencephalogram (EEG). These indices were examined in common marmosets exposed to a range of doses of the organophosphorous sheep dip, diazinon. Cognitive performance was assessed by means of elements from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and radiotelemetry techniques were employed to monitor the electrocorticogram and sleep patterns. Data were collected for 12 months following intramuscular administration of a single dose of diazinon (10, 90 or 130mg.kg 1) or vehicle. Although high levels of erythrocyte acetylcholinesterase (AChE) inhibition (up to 82%) and short-term changes in sleep patterns were seen, there was no evidence of biologically significant long-term changes in any measures. The effects of multiple exposures, impurities or mixtures of OP compounds remain to be investigated.

Multiple vaccine and pyridostigmine interactions: Effects on cognition, muscle function and health outcomes in marmosets ☆

Following active service during the 1990/1991 Gulf Conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to armed forces personnel during the Gulf Conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from three aspects of the study, cognitive behaviour (performance of a touchscreen mediated discrimination task), muscle function (performance of a simple strength test) and general health. There were no marked long-term changes in cognition, muscle function or health that could be attributed to vaccines and/or PB administration. Statistical differences related to treatments were only observed in two aspects of cognition and one of clinical chemistry. These changes were transient in nature and their magnitude were minor and, in consequence, was not regarded as having long-term biological significance.

A simple method for assessing muscle function in common marmosets

A novel method of assessing muscle function in the common marmoset was developed as part of a multidisciplinary long-term study. The method involved home cage presentation of a weight-pulling task. Over a 4–5 month period, 38 of 42 animals were successfully trained to displace weights of up to 920 g (mean 612±20 g). Performance, following initial training, was stable and independent of gender or body weight.

Author’s reply - PON1 and low-dose sarin in marmosets

interest and warrant further investigation, where practicable. The authors would like to re-emphasize that one sarin-treated marmoset which showed a progressive course in beta 2 EEG activity over the course of the study, showed no performace deficits on the complex tests of cognitive behaviour presented during this time. This suggests no marked functional disruption in this subject. In addition, the animal’s control levels of cholinesterase inhibition and time course of recovery were not different from those of the other animals in the group. It is also worth reiterating that a single animal was responsible for a non-significant downward trend in the beta 1 band of the EEG recorded from the saline control group during the course of the study. Again, this animal showed no performance deficits on the complex tests of cognitive behaviour presented. 88 JOURNAL OF PSYCHOPHARMACOLOGY 14(1)