If the vocalizations of rats in response to noxious stimulus are complex and their behavioral significance poorly understood, they can be very useful and interesting for assessing pain in animals. This review indicates that vocalizations consist of different components more or less link to the direct response to a painful stimulus but all induced in its context. The audible peeps were only recorded in context of pain and seems directly linked to nociception. Chatters and ultrasonic vocalizations may reflect the emotional response to pain.
A great deal of studies show that many factors such as noise, light, presence of human beings can disturb the physiology and the behaviour of animal that are housed and manipuled in laboratory, in modifying their welfare state. According to some authors, to house animals in an enriched environment increases their ability to adapt to the environment and lowers their level of stress and emotion in new situations. The aim of the study here presented and carried out in the animal house of the Sanofi-Synthelabo centre is to determine the influence of the reproduction of dawn and dusk as well as the presence of temporary music in the housing room on the rat's behaviour at various moments said to be stressful for it. The results show that the enriched environment decreases the rat's reactivity in housing rooms but has only little influence when rats are taken out to be manipulated and has no influence on the results obtained during an anxiety test (Elevated Plus-Maze).
Dexamethasone, and some other glucocorticoids, are known to be inducers of cytochrome P-450 3A isoform (CYP3A). However, little information is found in the literature about the adverse effects related to such inducing treatment, especially on the important body weight loss which makes treated animals more vulnerable to subsequent treatment with other drugs. In view to obtain adequate CYP3A induction in male and female rats while minimizing body weight loss and mortality after further in vivo treatment with other drugs, we successively varied cumulated dosage (300 to 600 mg/kg), concentration (100 to 150 mg/kg/day), duration of DEX administration (3 or 4 days), and delay before sacrifice after last DEX administration (24 to 72 h), and determined CYP3A activity by western blot. Results show that a single daily p.o. administration of 100 mg/kg DEX during 3 days (cumulated dosage = 300 mg/kg), with sacrifice 24 h after last DEX administration, produces an acceptable CYP3A induction (vs undetectable amounts in controls) with a minimum body weight loss.
The sales of medical devices (MD) in the european community are ruled by European directives (DE 90/385 and DE 93/42) which refer to several European norms (EN 90-993, EN 1441, EN 46010). There are many references to the necessity and modalities of animal testing of the MD in the European directives and normes. We reviewed these points and their consequences for interventional devices.
In this study we show that noradrenaline (NA) is able to trigger a motor rhythmic activity in the spinal cord of newborn rat, but which is not related to a locomotor activity. By the use of specific adrenergic agonists, we have determined that this rhythmic activity is mediated by the alpha 1 receptors of NA. In a second step, we have tested the NA effects on rhythmic locomotor-like activity induced by an excitatory amino-acid (NMA) in the order to see if NA or its agonists modulate this locomotor network activity. It appears that NA itself does not modify the rhythm induced by NMA alone. In contrast, the alpha 1 agonists decreased the motor period while the alpha 2 agonists increased it. Concerning beta agonists, they appeared to increase the motor period, and in the same time to induce a locomotor rhythm more regular. Altogether, these experiments show that if NA does not play a direct role in the initiation of locomotor activity in the rat, it is able to largely modulate the ongoing activity depending on which receptors are activated.
In order to work with animals treatened with extinction, it is necessary to use methods that reduce stress as much as possible. On Curacao, in the Netherlands Antilles, two endangered species of nectar-feeding bats pollinate columnar cacti and thus allow the survival of the endemic fauna that depends on the fruits. In the past, bats, which are very fragile animals, have been abused by researchers. Yet, by using simple techniques, I was able to release in good health each individual captured, and to discover information essential to the survival of the island's natural ecosystem. Scientifists must show patience, creativity, and integrity in the study of sensitive and intelligent animals.
A model of cerebral ischemia by cauterisation of the middle cerebral artery was reproduced in Sprague-Dawley rats. Pre- and 24h post-surgical neurological evaluations using a battery of motor and sensory behavioural tests were compared to correlate behaviour changes and the size of the cerebral ischemia. Motor and sensorimotor evaluations have a positive correlation of 0.66 with the size of cerebral ischemia (P< 0.02). Meanwhile, sensory evaluation only have no predictive value of the extent of cerebral damage (r = 0.18, p = n.s). These results are in acoord with previous published findings when using a battery of sensory and motor tests. However, our results show that motor tests only are sufficient to predict and evaluate the size of cerebral ischemia following the cauterization of the MCA.
Therapeutic needs in the field of analgesia are mainly focused on the relief of chronic pain sustained by either inflammatory or neuropathic mechanisms. The high diversity of physiopathological mechanisms supporting chronic pains make necessary to use many different animal models, a point that is ethically disputable. In such a way, it may he valuable to characterize the pharmacology of compounds using in vitro assays before testing in vivo those having been selected, In parallel to pharmacological evaluation, it is proposed to add physicochemical, pharmacokinetic and metabolic ir, vitro assays in the purpose to predict the availability of new chemical entities in the body. Furthermore, recombinant methodologies are now allowing to work with human targets previously introduced into competent cell lines. The ultimate goal consists to get the highest confidence in predicting in vivo activity and thus, limit the number of molecules to he tested in animals.
We developed an alternative and original method to generate immuno-enzymatic tracers, which avoid the difficulties characterizing chemical procedures. Our strategy consists in designing hybrid genes between the DNA ending for Various proteic antigens or antibody fragments and the gene encoding the bacterial alkaline phosphatase, then to produce them in the bacteria Escherichia coli, Numerous recombinant tracers between proteic antigens having variable sizes and structural complexities and the alkaline phosphatase were thus obtained, Similarly, we built and produced scFv/ and/or Fab/PhoA hybrids. All these recombinant compounds are fully bifunctionals, and susceptible to replace conventional immuno-enzymatic tracers.
The use of Large White pig aloud the realisation of a chronical myocardial infartion model, by a circomflex artery ligation, comparable with an ischemical injury. In spite of a hight death rate (30 %) cause by ventricular fibrillation, it has been possible to obtain infarction representing 10,7 % of the left ventricular mass. The result of this contraction failure is a 44.4 % augmentation of the end systolic volum and a 52 % fall of the ejection fraction. The different periods of this protocol are here exposed.
The assessment of the effectiveness of analgesics is strongly based on observational data from behavioural tests. These tests are interesting to give a quantization of the effect of the drugs on alive animals but their use is subjected to several difficulties : (1) many tests are difficult to analyze as they are only based on the evaluation of a reflex response, (2) the tests dealing with more integrated responses are also more difficult to use and closely depends on experimenter's subjectivity. Automation can contribute to optimise these tests. The use of signal processing devices allows the automated measurement (and thus objective) of a pain related parameters (amplitude of a reflex, vocal emission intensity). Video image analysis allows the quantization of more complex behaviours (pain-induced specific motor behaviours) as well as several meaningful information during a same experimentation (exploratory behaviour, total motor activity, food behaviour). Moreover, these methods make possible to get a more objective measurement, to reduce animal experimenter interactions, to ease system use, and to improve effectiveness. The prospects to work in this field are multiple : continuation of the attempts at an automation of the behaviours specifically induced by chronic pain; development of actual animal pain monitoring based on analysis of specific and non specific behavioural modifications induced by pain. In this context, the automation of the behavioural analysis is likely to make possible real ethical progress thanks to an increase in the test's effectiveness and animal pain. Nevertheless, there is some limits due to technological problems and characteristics of the behavioural expression of pain.
As soon as medicines have get a marketing authorisation,they are controlled by manufacturers and Health Authorities. In France, the Agence du Medicament is in charge of the quality control of medicinal products for human use. Three parameters have to be taken into account : qualitative and quantitative conformity to the formula, evaluation of non toxicity (security controls) and quantification of activity. The two last points are animal large consumers. All these tests are in accordance with registration files, Pharmacopoeias, WHO recommendations for biological substances and guidelines for European Batch Release Procedure.
We have studied pup-directed maternal behavior in mice carrying a germ line null mutation of the prolactin receptor gene. Heterozygous nulliparous and primiparous females and homozygous nulliparous females exhibit a profound deficit in maternal care when challenged with foster pups. Morris maze studies revealed normal configural learning in heterozygous and homozygous animals. Olfactory function was tested in an aversive conditioning paradigm, confirming that heterozygous and homozygous prolactin receptor mutant mice are not anosmic. This studies clearly establish the prolactin receptor as a regulator of maternal behavior.
