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Biomedical subjects

A U Höglund

Publications and source records attributed to A U Höglund.

16 recordsLinked to original sources

Human-animal interactions and animal welfare in conventionally and pen-housed rats.

The main aim of the present study was to explore the significance of large group/greater pen housing (PH) versus standard Makrolon caging (ST) in three behaviour tests related to human-animal interactions in the adult male laboratory rat. The rats' perception of human interaction was tested in three behavioural tests, of which two reflected common practical procedures, capture and restraint, whereas the third was a human approach test in a Y-maze. The rats' anticipatory reactions to handling and the reactions to restraint did not differ between groups, but the ST rats approached a human hand more quickly than did the PH rats (P < 0.01). Although food intake did not differ, ST rats gained more weight (P < 0.01) and had higher total cholesterol values (P < 0.01) than PH rats. In conclusion, this study shows that housing rats in large groups in an enriched environment did not influence their anticipatory reaction to handling in normal handling situations. However, as the PH rats tended to have a longer approach latency than ST rats in the Y-maze there might be underlying differences in appraisal that are not detected in practical situations. In addition, the PH rats weighed less and had lower total cholesterol values than ST rats and their urine corticosterone values were higher. These effects are suggested to be due to higher physical activity in the PH rats, and the implications of this on the animal as a model is discussed.

Animal Husbandry↗

Evaluation of individually ventilated cage systems for laboratory rodents: occupational health aspects.

New ventilated caging systems for laboratory animals were compared with conventional caging regarding allergen distribution, ergonomic suitability, cage environment and animal welfare. This paper presents occupational health evaluations. Mice were placed in individually ventilated cage (IVC) systems, a ventilated cabinet, and in cages on open shelves (conventional husbandry). The IVC systems were studied at negative and positive airflow. Aeroallergens were sampled on filters (n = 204, including controls) in undisturbed rooms and during cage changing. Concentrations of mouse urinary allergen (Mus m 1) in filter eluates were measured using sandwich ELISA. An ergonomic evaluation was performed with measurement of traction forces. Staff exposure during cage changing was high in all systems, range 116-4430 ng Mus m 1/m3. In undisturbed animal rooms, allergen levels were orders of magnitude higher when using conventional caging compared with ventilated systems; P < 0.001. At positive pressure both IVCs leaked allergen (median Mus m 1 concentration was < 0.08 ng/m3 at negative, but 6.5 ng/m3 (IVC1) and 0.8 ng/m3 (IVC2S) at positive pressure). The IVC systems had ergonomic disadvantages compared with the conventional husbandry and the ventilated cabinet, for instance with cages in unsuitable working heights. Ventilated husbandry solutions reduce levels of airborne allergen substantially at negative pressure, but are ergonomically less suitable. To prevent allergen exposure during cage changing, we propose that this procedure should be performed under ventilated conditions. Producers and users must cooperate in optimizing animal caging systems for both animals and staff.

Air Pollutants, Occupational↗

Evaluation of individually ventilated cage systems for laboratory rodents: cage environment and animal health aspects.

The use of individually ventilated cage (IVC) systems has become an attractive housing regime of laboratory rodents. The benefits of IVC systems are, reportedly, a high degree of containment combined with relative ease of handling, and a high degree of protection from allergenes. In the present study we tested whether two IVC systems (BioZone VentiRack, IVC1 and Techniplast SealSafe, IVC2S), in which we held mature male NMRI mice, were constructed to maintain a constant differential pressure, positive or negative, during a prolonged period of time. We also measured ammonia (NH3) concentrations after about 2 weeks of use, and CO2 build-up during a 60 min simulated power failure situation. In addition, animal weight development and bite-wound frequency were recorded (Renström et al. 2000). From the present study it is concluded that the IVC1 air handling system provides a more uniform and balanced differential pressure than the IVC2S. Both systems effectively scavenge NH3 when bedding material is not soaked by urine. Although the IVCs are dependent on the continual function of the fans to work properly, it seems unlikely that CO2 concentrations increase to hazardous levels, as a result of a one hour power failure, with the type of cages used in this study. Differences in weight development and bite-wound occurrence were noted between the two IVC systems. Causes for these differences could not be established and need more investigation.

Air Conditioning↗

Undergraduate and postgraduate students' responses to mandatory courses (FELASA category C) in laboratory animal science.

The results from the analysis of the course evaluations from FELASA category C compulsory courses in laboratory animal science at Uppsala University showed that the students realize that theoretical knowledge of the subject and practical skills are of great importance to the success of their future research involving animal experiments. All the subjects and elements of the course, in particular the practicals on animal handling and procedures using live anaesthetized animals, were fully appreciated by the students.

Adult↗

Effects of microdialyzed oxotremorine, carbachol, epibatidine, and scopolamine on intraspinal release of acetylcholine in the rat.

Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1-C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 microM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 microliter/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100-1000 microM), carbachol (1 mM), and epibatidine (50-5000 microM) enhanced but scopolamine (50-200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED(50) = 118 microM) and epibatidine (ED(50) = 175 microM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain.

Acetylcholine↗

Quantitative autoradiography with short-lived positron emission tomography tracers: a study on muscarinic acetylcholine receptors with N-[(11)C]methyl-4-piperidylbenzilate.

The present work demonstrates quantitative autoradiography by using positron emission tomography tracers and storage phosphorimaging plates. The uptake and association of [(11)C]N-methyl-4-piperidylbenzilate was measured in rat brain tissue cryosections of various thicknesses. The signal increased with increasing section thickness, but only in 10-micrometer-thick sections did the binding reach the steady state during a 50-min observation time. This violation of the equilibrium condition, potentially combined with perfusion limitations, leads to erroneous increased binding-site density and decreased affinity in the 25- and 50-micrometer-thick sections. For better imaging of receptor distribution it is reasonable to use thicker sections. For quantitative analysis of receptor-binding parameters, the specific properties of ligands at different thicknesses of cryosections need to be considered. Evidence is provided that the nonselective muscarinic antagonist N-methyl-4-piperidylbenzilate binds preferentially to the M(4) subtype of muscarinic acetylcholine receptors.

Animals↗

Aspects on tail-flick, hot-plate and electrical stimulation tests for morphine antinociception.

The objective of this study was to compare the results of three nociceptive tests, tail-flick, hot-plate and electrical stimulation vocalisation, reflecting the responses from different sites in the CNS. A subcutaneous morphine dose (5 mg/kg) was administered to three parallel groups of rats in which the nociceptive response was measured by one of the three methods. The baseline decreased during the period of measurement for the hot-plate test, but remained stable for the other methods. The spinally mediated tail-flick response was more sensitive to the morphine effects as compared to the supraspinally mediated hot-plate and electrical stimulation vocalisation responses. The electrical stimulation vocalisation-test demonstrated more even effect-time profiles and less variability among the rats than did the tail-flick and the hot-plate methods. In the tail-flick group, 59% of the observations attained the cut-off latency at this morphine dose, leading to underestimation of the peak effect, the area under the effect curve (AUEC), and the variability among the rats. In the hot-plate group, 13% of the observations were at the cut-off latency, and 2% in the electrical stimulation vocalisation group. Different ways of presenting the data are discussed. In conclusion, the test selected for measuring the nociceptive response will influence the effect-time profile and subsequently any pharmacodynamic parameters describing it.

Analgesics, Opioid↗

M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord.

Muscarinic receptors in the spinal cord have been shown to mediate antinociception and alter blood pressure. Currently, there is much interest in identifying which muscarinic receptor subtypes regulate these functions. Toward that end, this study aimed to identify and localize the muscarinic receptor subtypes present in spinal cord using in vitro receptor autoradiography with [3H]-pirenzepine and [3H]-N-methylscopolamine. The results showed that M2 binding sites were distributed throughout the dorsal and ventral horns, whereas M3 binding sites were localized to laminae I to III of the dorsal horn. Only background levels of M1 binding sites were detected. Saturation binding assays using [3H]-pirenzepine in spinal cord homogenates confirmed the absence of M1 receptors. Competition membrane receptor assays using [3H]-N-methylscopolamine and the unlabeled antagonists pirenzepine, 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5, 11-dihydro 6H-pyrido(2, 3-b)(1, 4) benzodiazepine-one, methoctramine, and methoctramine in combination with atropine corroborated the autoradiographic findings and also revealed the presence of M4 binding sites. The finding that M2 and M3 binding sites were localized to the superficial laminae of the dorsal horn where nociceptive A delta and C fibers terminate suggests the possibility that either or both of these muscarinic receptor subtypes modulate antinociception. The present demonstration of M4 binding sites in spinal cord is consistent with the possibility that M2 and/or M4 receptors are involved in the regulation of blood pressure at the spinal level.

Animals↗

The long-term effects of 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) on copulatory and exploratory behaviour in male rats.

The long-term effects of low doses of the 5-HT1A-agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied to assess differences in the development of subsensitivity in 8-OH-DPAT-induced behavioural responses. Male rats received 33 or 100 micrograms/kg per day s.c. for 8 or 15 days. The chronic treatment did not alter the facilitatory effects of 8-OH-DPAT on male copulatory behaviour. In contrast, the effects on exploratory activity and the induction of flat body posture observed after the acute treatment were attenuated by prolonged administration of 8-OH-DPAT. The results presented indicate that gonadal hormones are involved in 5-HT receptor regulatory mechanisms.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Increased investigative activity after presynaptic dopaminergic stimulation measured by a fixed-interval recording procedure.

A fixed-interval recording procedure was used to study the effects of catecholaminergic agonists and antagonists on the exploratory behaviour pattern in male rats. One particular element of this pattern, the investigative behaviour, was found to be sensitive to drugs acting on both noradrenaline and dopamine receptors. An increase in investigative activity (IA) and a slight decrease in the other exploratory (OE) activity was caused by alpha-methyl-p-tyrosine. The alpha 2-receptor agonists clonidine and B-HT 933 decreased both the IA and the OE activity. These effects were counteracted by yohimbine. Activation of presynaptic dopamine receptors by low doses of apomorphine (less than or equal to 0.2 mg/kg) and B-HT 920 resulted in significant increase in IA and a decrease in OE activity. Higher doses of apomorphine (0.7 and 1.0 mg/kg) decreased or abolished IA but increased OE activity. We assume this effect to be due to postsynaptic receptor stimulation. Pretreatment with haloperidol counteracted the effects of apomorphine and B-HT 920. An increase in IA is probably due to a decrease in dopaminergic activity, which can be induced by presynaptic receptor activation. The decrease in IA after presynaptic noradrenergic stimulation cannot at present, however, be related to a specific influence, since the possibility of general effects on locomotion cannot be ruled out. The increase in IA observed after presynaptic dopaminergic activation and the fixed-interval recording procedure may be valuable instruments in the search for selectively acting compounds with dopaminergic activity.

Adrenergic alpha-Agonists↗

Facilitatory effects of monoamine synthesis inhibitors on lysine-vasopressin induced changes in the exploratory behaviour pattern of male rats.

The possible interaction between vasopressin and monoamines in the regulation of exploratory behaviour was investigated. Treatment with lysine-vasopressin (LVP) influenced this behaviour. In particular, the investigative activity was enhanced. The dose-response relationship of LVP was non-linear. The catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (alpha-MT, 100 mg/kg) also increased the investigative activity, indicating a suppressive influence of catecholamines on this behaviour. alpha-MT pretreatment potentiated the effect of LVP within certain dose levels. The dose-response relationship for the peptide effect on the investigative activity was shifted towards the left. Treatment with the serotonin biosynthesis inhibitor para-chloro-phenylalanine (PCPA) (100 + 50 + 50 mg/kg) also enhanced the investigative behaviour and potentiated the action of LVP similarly to alpha-MT. It is suggested that the action of LVP on the exploratory behaviour in rats can be modified by monoamines.

Animals↗

A video interface for behavioural recordings with applications.

An interface which can transmit information from a TV camera to a minicomputer is described. The interface delivers addresses significant for the position of an animal in an observation arena. These addresses are then treated by a minicomputer assembler program. In our application, the length of visiting (duration), frequency of visits and latency of first visit to a specified field are recorded, together with an activity variable. The high IR sensitivity of the camera makes it possible to record the position of the animal relative to certain environmental objects under conditions of dimmed light.

Animals↗

Effects of lysine-vasopressin in an exploratory behaviour test situation.

Changes in the exploratory behaviour pattern in rats were studied over a period of eight weeks. Certain characteristics emerged during repeated exposure to the same environment. The activity of "investigating" behaviour increased, while rearing activity decreased. We suggest that these changes reflect habituation by the animal to the test situation. Administration of lysine-vasopressin (LVP; 5.0 micrograms/kg SC) resulted in some alterations of the exploratory behaviour pattern, but no other behaviours than those observed without drug treatment were seen. The administration of LVP resulted in a higher performance of "investigating" behaviour. Since the change in the exploratory behaviour pattern after LVP administration was similar to that during repeated exposure to the test situation, we conclude that the LVP treatment influenced processes of habituation.

Animals↗

Exploratory and socio-sexual behaviour in the male laboratory rat: a methodological approach for the investigation of drug action.

There is an increasing demand for appropriate methods for analysing the pharmacological and toxicological action of chemical agents on behavioural patterns. The present study describes a non-instrumental approach to the study of exploratory and socio-sexual behaviours in the laboratory male rat. The behaviours were differentiated in terms of latency of onset, incidence, frequency and duration. Castrated and intact males were tested under three defined test situations. One test was focused on exploratory behaviour and two tests in which the male encountered an oestrous female or a castrated male were set up to study social and sexual behaviours. A multivariate statistical method was used to analyse differences in the behavioural profiles observed in the different tests. The data show that simultaneous recording of several spontaneous behaviours may be a useful technique for investigating how a compound influences behavioural processes.

Animals↗

A keyboard data collecting device for behavioural recordings.

A keyboard data collecting device which makes it possible to record the duration, frequency and latency of ten different forms of behaviour simultaneously via direct observation, is presented. The device is simple to operate and easily built even in laboratories without advanced electronic knowledge. It makes the handling of extensive amounts of data easy, since a punched tape output of ASCII-coded data is available for rapid computer processing.

Animals↗