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Biomedical subjects

R Dantzer

Publications and source records attributed to R Dantzer.

At least 181 records · Page 10Linked to original sources

Effect of floor area restriction upon performance, behavior and physiology of growing-finishing pigs.

Fifteen groups of eight pigs were allocated .34, .68 or 1.01 m2 lying area per pig between 25 and 100 kg live weight. These values were chosen in accordance with Petherick's model to prevent all pigs from lying in full recumbency (.68 m2/pig) or on their sternum and belly (.34 m2/pig). Productivity decreased in the groups of pigs allowed only .34 m2/individual from 20 wk following the beginning of the experiment (70 to 80 kg). Behavioral changes were observed as early as 8 wk after the beginning of the experiment (60 to 70 kg). Severe area restriction increased time spent at the feeder. Aggression did not vary as a linear function of area allocation. Analysis of the main behavioral activities over a 10-h observation period revealed higher feeding time and lower social activity in pigs kept at .34 m2/pig. Sternum resting was more frequent than resting on the side when body weight reached 60 to 70 kg. Pigs that were submitted to the lower area allocation displayed enhanced resistance of their pituitary-adrenal axis to the dexamethasone suppression test and enhanced reactivity to adrenocorticotropic hormone injection. These findings demonstrate that behavioral and physiological responses are earlier and more sensitive indicators of adaptation to the environment than productivity.

Animals↗

Modulation of mitogen-induced lymphoproliferation by cerebral neocortex.

The influence of the cerebral neocortex on the immunological status was studied in groups of C3H/He mice after lesioning the right or left fronto-parietal cortex. In left lesioned mice, mitogenesis induced either by phytohemagglutinin (PHA) or concanavalin A (Con A) was depressed by about 50% compared to controls. On the contrary, in animals with right lesions, T cell mitogenesis was enhanced by about 140% as compared to controls and by 220-300% as compared to that observed in left lesioned animals. Mitogenesis of B cells induced by lipopolysaccharide was modified by cortical lesions in exactly the same way as that of T cell proliferation although not reaching statistical significance. These results confirm the lateralization in the cortical modulation of the immune system.

Animals↗

Behaviorally conditioned suppression of mitogen-induced lymphoproliferation and antibody production in mice.

Conditioned immunosuppression was induced in C57BL/6 mice by pairing saccharin drinking (conditioned stimulus) with an i.p. injection of 250 mg/kg cyclophosphamide (unconditioned stimulus). Conditioned mice showed depressed mitogen-induced lymphoproliferation. This depression was significant for T-cell--but not for B-cell--proliferation. Mice also exhibited depressed antibody production against sheep red blood cells until 15 days after immunization. The kinetics of serum antibody levels suggest that conditioning amplifies the immunosuppressive effects of cyclophosphamide. Furthermore, we show in this report that a depression of cellular and humoral components of the immune system can be observed when conditioning is performed after immunization, the latter being not paired with the conditioned stimulus.

Animals↗

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats.

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.

Adrenal Glands↗

Pituitary-adrenal correlates of schedule-induced polydipsia and wheel running in rats.

To investigate the pituitary-adrenal correlates of schedule-induced behaviours, rats were submitted to a fixed-time 60-s schedule of food reinforcement, with free access to either a water spout or a running wheel. Schedule-induced water drinking (polydipsia) was accompanied by an important drop in plasma corticosterone levels, while wheel running resulted in a significant increase in plasma corticosterone concentrations. This contrast between the pituitary-adrenal consequences of schedule-induced drinking and wheel running was not due to functional differences between the two activities since wheel running was shown to display all the characteristics of schedule-induced activities, mainly excessiveness, differential time distribution and dependance on deprivation level and reinforcement rate.

Animals↗

Behavioral, physiological and functional aspects of stereotyped behavior: a review and a re-interpretation.

Stereotypies are repetitive actions that are fixed in form and orientation and serve no obvious purpose. Their occurrence in farm animals submitted to intensive husbandry has been interpreted to indicate inadequate environmental design or welfare. Over recent years, detailed descriptive studies have led to a better understanding of the organization and development of stereotypies, particularly in pregnant sows housed in tether stalls. Stereotyped behaviors appear to emerge from elements of initial defensive reactions of animals to their environment. They develop via a progressive narrowing of the behavioral repertoire, until only self-directed behaviors are displayed. Pharmacological studies suggest that performance of stereotyped behavior depends on the brain dopamine systems that are involved in selection and initiation of motor movements. However, generalization of these data to natural stereotypies is doubtful. Recent evidence favors an involvement of brain opioid peptides in stereotyped behavior of sows, although the exact mechanisms remain unknown. Stereotypies are typically observed in situations of conflict or frustration. They have been claimed to have an adaptive function, either by providing self-generated sensory stimulation to compensate for the lack of environmental stimulation, or by allowing animals to discharge their tension or anxiety. However, there is little evidence in favor of either interpretation. On the basis of present knowledge, it is proposed that stereotyped activities gain strength because of the positive feedback effect of sensory stimulation on their underlying control systems, which leads to a progressive sensitization of these neural systems. Stereotypies would then be simply the outward expression of an activation of lower brain structures controlling motor behavior which occurs in the absence of normal inhibitory control by higher nervous functions.

Animals↗

The pig as a model for behavioral research.

Behavioral studies of pigs have been carried out mainly for applied purposes, ranging from improvement in animal production to animal welfare issues. Since this research generally has made use of easy to measure behavioral end points, there is a relative lack of quantitative descriptions of behavioral sequences and of studies of mechanisms. For behaviorists, pigs present many interesting characteristics in their sensory-perceptual world and in the expression of some of their activities. Therefore, there is potential for more detailed behavioral studies in this species and some possibilities are presented.

Animals↗

Stress-induced analgesia in pigs.

In order to assess pain sensitivity in pigs, the tail-withdrawal reflex induced by immersing the tail into warm water was used. Reaction times were found to be a negative function of water temperature. They were not modified by 1 mg/kg morphine or naloxone. Higher doses of morphine (5 mg/kg) induced excitation which interfered with the assessment of the tail-withdrawal reflex. Low doses of xylazine (0.1-0.2 mg/kg) decreased reaction times while clearly sedative doses (10 mg/kg) had no effect. Various stressors (handling, exposure to a new environment, shock delivery, social isolation) enhanced reaction times and this increase was not blocked by naloxone.

Analgesia↗

Relevance of some behavioural criteria concerning the sow (motor activity and water intake) in intensive pig farming and veterinary practice.

In the pregnant tethered sow, water intake and motor activity were found to be related to urinary problems and productivity. Therefore, further studies were undertaken on these points. The 258 pregnant sows from eight breeding finishing herds were submitted to water intake control and the investigation of motor activity was performed on 125 pregnant sows from 6 herds. Despite the same process of water supply, the intake varied a lot from sow to sow (mean: 17 litres/day/pregnant sow, (sigma = 6.9 l). The major part of water was drunk during feeding time. The following factors were found associated with water intake: body condition, lameness, parity, stage of pregnancy. The relations between water intake and urine composition were assessed. A low water intake was close related to high urine gravity and to abnormalities (crystals, proteinuria, bacteriuria). The pregnant tethered sows spent an average time of 250 min in the standing position. A diurnal rhythm was clearly observed and it was synchronized by feeding time. The following factors were found to be related to the standing time: parity, body condition, lameness. The frequency of standing up per 24 hours was not related to the total standing time. Under farm husbandry, standing time is rather inconstant in individual sows on subsequent days. Since photo cell apparatus cannot be used as a routine in veterinary practice, we have looked for a more simple method: the position of the sows one hour after feeding time. This index gave an accurate view of the total standing time and represented a practical parameter for epidemiological purposes. The relevance of measuring water intake and motor activity in veterinary practice is discussed.

Animal Husbandry↗

Analysis of the dual mechanism of ACTH release by arginine vasopressin and its analogs in conscious rats.

Plasma ACTH and/or corticosterone levels were measured in conscious rats 30 min after subcutaneous administration of arginine vasopressin (AVP), oxytocin (OT) and various analogs with a large range of activity on the vasopressor (V1), antidiuretic (V2) or oxytocic receptors. The comparison of their dose-response curves indicated that two different mechanisms are involved in the release of ACTH by neurohypophysial peptides and their analogs. AVP itself and a specific vasopressor agonist (Phe2, Orn8, OT) displayed a similar, high slope dose-response curve. Non-vasopressor analogs, such as dDAVP were characterized by a low slope dose-response curve. Furthermore, dDAVP potentiated CRF and neither its own ACTH-releasing action nor its potentiation of CRF were sensitive to previous VI- or V2-receptor blockade. These results, together with other available data, are interpreted as indicative of the existence of two mechanisms of action for ACTH release by AVP and its analogs in vivo: an indirect action via endogenous CRF release, mediated by a VI receptor mechanism, and a direct action on the pituitary, shared by dDAVP and other non-vasopressor analogs, with receptor characteristics different to both the V1 and the V2 classical types.

Adrenocorticotropic Hormone↗

Effects of naloxone, beta-endorphin and ACTH on acquisition of schedule-induced polydipsia.

A series of three experiments examined the possible involvement of endogenous opioid peptides in the development of schedule-induced polydipsia in rats. Repeated pretraining treatment with 2 mg/kg naloxone impaired acquisition of schedule-induced polydipsia, whereas the same treatment injected after training increased drinking. This later effect was time dependent, since a 30-min delay in the injection of naloxone resulted in a disappearance of its effect. Post-training injections of 10 micrograms/kg beta-endorphin or ACTH delayed the development of drinking. These findings are consistent with the hypothesis that endogenous opioid peptides modulate the development of schedule-induced polydipsia.

Adrenocorticotropic Hormone↗

Specificity of aversive stimulus properties of vasopressin.

Rats injected SC with arginine vasopressin (AVP) following consumption of a milk solution developed a marked aversion to the taste of this solution. An analog of vasopressin devoid of pressor activity, dDAVP, was unable to induce conditioned taste aversion. The aversive stimulus properties of AVP were blocked by the vasopressor antagonist dPTyr(Me)AVP. This antagonist did not block apomorphine-mediated conditioned taste aversion. These results demonstrate that AVP induces conditioned taste aversion by interacting with vasopressor-like receptors.

Animals↗

Conditioned taste aversion suppresses induction of delayed-type hypersensitivity immune reactions.

Conditioned taste aversion was induced in mice by pairing saccharin drinking with an intraperitoneal injection of lithium chloride, a toxic but nonimmunosuppressive drug. Conditioned mice showed not only suppressed saccharin drinking but also a 75% reduction in the induction of delayed-type hypersensitivity immune responses to low doses of sheep erythrocytes. This effect was observed with doses of lithium chloride which had no effect of their own on immune functions. In addition, a reduction in water consumption was not responsible for the reduced immune response of conditioned mice since the immune responses of water deprived mice did not differ from those of nondeprived mice. Conditioned mice exposed to saccharin had higher plasma levels of glucocorticoids than nonconditioned mice, suggesting that the experience of being reexposed to a taste paired with lithium chloride was perceived as aversive. These data demonstrate that alterations in immune functions can be induced by a conditioned taste aversion procedure independently of any immunosuppressive drug.

Animals↗

The effect of 6-OHDA lesions of the lateral septum on schedule-induced polydipsia.

In this study the relationship between 6-hydroxydopamine lesions of dopaminergic innervation of the lateral septum and schedule-induced polydipsia was examined. Animals with lesions were found to have a significant increase in water intake during a test involving an intermittent schedule of food delivery. Additional experiments with these animals showed that lesions had no effect on: (i) spontaneous drinking, the amount of drinking after 24 h food or water deprivation, water intake following a hypertonic saline challenge; (ii) eating behavior with or without food deprivation; and (iii) spontaneous locomotor activity. This increase in adjunctive behavior is discussed in the light of an enhanced frustrative effect induced by the septal lesions.

Animals↗

Effects of post-trial injection of beta-endorphin on shock-induced fighting are dependent on baseline of fighting.

The effects of repeated post-trial administration of 10 micrograms/kg beta-endorphin on the development of mutual fighting in pairs of rats submitted to various intensities of electric shock were investigated. beta-Endorphin blocked the development of fighting responses when a low footshock intensity was used, but facilitated it when a high shock intensity was delivered. A detailed analysis of the relationship between shock intensity, baseline of fighting, and effects of beta-endorphin showed that the effects of beta-endorphin were dependent on the behavioral baseline rather than on shock intensity per se.

Animals↗

Arginine vasopressin, stress, and memory.

Arginine vasopressin (AVP) has been shown to have several non-renal actions including the potentiation of learned avoidance behavior in rats and improvement in cognitive functioning in humans. Research in our laboratory has confirmed these behavioral effects in rats using both peripheral and central injection of AVP. We have begun to examine the physiological basis for these effects. Peripheral administration of a vasopressor AVP antagonist reversed the prolongation of extinction produced by peripherally administered AVP in both active and passive avoidance, but also reversed the aversive unconditioned effects of AVP. However, central administration of the vasopressor AVP antagonist reversed peripheral effects of AVP only at doses shown to act peripherally to reverse vasopressor effects of AVP. An osmotic stress in doses known to liberate endogenous AVP mimicked the behavioral effects of exogenously administered AVP, and this stress effect was reversed by the AVP antagonist. These results support our hypothesis of separate but parallel AVP systems in the pituitary and brain with a role in behavioral adaptation to certain types of stress.

Animals↗

Ethyl loflazepate: a prodrug from the benzodiazepine series designed to dissociate anxiolytic and sedative activities.

Ethyl loflazepate (Victan) is an original 1,4-benzodiazepine (BZD) being used as a potent, nonsedative, minor tranquillizer. Ethyl loflazepate was designed to be a prodrug that would gradually release within the organism an active 1,4-BZD. It was hypothesized that this type of pharmacokinetic profile would dissociate anxiolytic from sedative activities. Previously published pharmacokinetic studies performed in rats, baboons and humans have confirmed that ethyl loflazepate gradually releases in the plasma an active 1,4-BZD, descarboxyloflazepate. In the present study, the activity of ethyl loflazepate and its main plasmatic metabolites were examined in rodent models predictive of anxiolytic, anticonvulsant, myorelaxant and sedative properties. The activities of ethyl loflazepate and its metabolites were compared to those of reference BZDs: diazepam, bromazepam, nitrazepam, flunitrazepam, lorazepam, clorazepate. Ethyl loflazepate and its metabolites revealed the typical profile of activity of minor tranquillizers. The activity of ethyl loflazepate was long-lasting. The overall anxiolytic potency of ethyl loflazepate was similar to that of diazepam but ethyl loflazepate appeared to be less sedative than diazepam. Thus in the approach-avoidance conflict procedure in rats the threshold anxiolytic doses were 1 and 2 mg/kg i.p. for ethyl loflazepate and diazepam, respectively, whereas the threshold sedative doses were 16 and 8 mg/kg i.p., respectively. In vitro ethyl loflazepate exhibited a weak affinity for the BZD receptor site. In vivo ethyl loflazepate displaced [3H]-flunitrazepam from mice brain membranes with a potency comparable to that of lorazepam. In vitro, descarboxyloflazepate, the main plasmatic metabolites of ethyl loflazepate, revealed a 4-fold greater affinity for the BZD receptor than diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of shock-induced fighting and social factors on pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats.

The present experiment investigated changes in pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats exposed to electric shocks in pairs or individually, in comparison to animals receiving no shock and tested in pairs or alone. Pairs of rats repeatedly exposed to electric shocks displayed a lower activation of the pituitary-adrenal system but a stronger activation of the sympathetic-adrenal medullary system than rats shocked individually. There was no differential release of prolactin according to the social setting in which shock occurred. Social factors by themselves influenced plasma corticosterone levels but not plasma levels of ACTH and prolactin nor catecholamine synthesis. The results are discussed in relation to the postulated beneficial effects of fighting on physiological activation produced by electric shock.

Adrenal Medulla↗