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D F Bull

Publications and source records attributed to D F Bull.

12 recordsLinked to original sources

Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation.

The present study investigated the role of sympathetic innervation of the spleen in conditioned suppression of a contact hypersensitivity (CHS) reaction. Behavioral conditioning was achieved by pairing saccharin drinking solution (conditioned stimulus, CS) with injection of cyclosporin A (CsA, 20 mg/kg; unconditioned stimulus, UCS). Four days after sensitization of the animals by application of a 5% 2,4-dinitrochlorobenzene (DNCB) to abdominal skin, the animals were challenged by applying a 1% DNCB solution to the ear. The CHS response was monitored by measuring the degree of ear swelling. Saccharin re-presentation reduced ear swelling to a magnitude that approached that achieved by CsA treatment. Histological examination demonstrated that the conditioned reduction of ear swelling was produced by a reduced leukocyte infiltration of the ear. Prior sympathetic denervation of the spleen did not alter the conditioned suppression of the CHS response. These data indicate that behavioral conditioning using CsA produces alterations of CHS that, unlike conditioned prolongation of heart allograft survival, are independent of sympathetically regulated conditioned alterations in the spleen.

Animals↗

The effects of lipopolysaccharide (LPS) on the fever response in rats at different ambient temperatures.

There is a complex interplay between the immune system, nervous system, and sleep. When an organism is challenged with lipopolysacchride (LPS), the immune system is stimulated, producing a fever response that is independent of ambient temperature, and an increase in slow-wave sleep (SWS). The study investigated sleep patterns of immune-challenged rats during the light phase cycle to determine the effects of various ambient temperatures. It was hypothesised that fever response would occur independently of ambient temperatures. Also, the febrile response would be monophasic, and there would be an increase in slow-wave sleep (SWS) and a decrease in rapid-eye-movement (REM) sleep. Thirty Wistar rats were randomly placed in 3 different ambient temperature groups, 22 degrees C, 15 degrees C, and 30 degrees C. Within each of these conditions, the same subjects served as control and experimental groups. Four animals were placed in 4 subsections of 2 standard boxes that were placed in the ambient-temperature box. The electrodes were connected to the analog to digital computer board, where all the data was processed and stored on a hard drive. The animals were injected I.P. with saline and recorded for a period of 6 h to establish a baseline. On Day 2, the same animals were injected I.P. with LPS and recorded for 6 h to determine the febrile effects of LPS on the immune system; the same procedure was repeated in the other ambient temperatures. The results have shown that animals experienced a monophasic fever response in low and normal temperatures, but not in the high temperatures. Although there was no increase in SWS, there was a significant decrease in REM sleep in 3 groups.

Animals↗

Behavioral conditioning of lipopolysaccharide-induced anorexia.

One manifestation of the acute phase response, sickness behavior, is now considered an important response in the organism's overall attempt to reinstate homeostasis. This report aimed to determine whether the sickness behavior of anorexia was conditionable using the conditioned taste aversion paradigm. To investigate this phenomenon, lipopolysaccharide (LPS) (100 micrograms/kg) was used as the unconditioned stimulus, and was paired with a novel 1% saccharin solution (conditioned stimulus). Upon conditioned stimulus representation, the anorectic effects of LPS were observed. These data are consistent with recent literature showing acute phase events to be conditionable.

Animals↗

Modification of body temperature and sleep state using behavioral conditioning.

Previous research has demonstrated the conditionability of events within the acute-phase response. This study examined whether two such responses, fever and sleep alterations, were conditionable in the rat during the dark photoperiod. The experimental animals were administered a novel saccharin solution as the conditioned stimulus (CS) in conjunction with lipopolysaccharide as the unconditioned stimulus (UCS). This group displayed significantly higher body temperatures than controls upon saccharin representation, 7 days after the original CS-UCS pairing. The experimental animals additionally displayed a conditioned increase in slow wave sleep (SWS); however, the LPS-induced reduction in rapid eye movement (REM) sleep was unable to be reenlisted. Similar to the acute-response, the conditioned alteration in SWS appeared to be due to an increase in episode frequency, rather than duration. These results suggest that the multiple acute-phase events may be simultaneously conditionable, producing an optimum environment for pathogen elimination.

Acute-Phase Reaction↗

Behaviorally conditioned anorexia: role of gastric emptying and prostaglandins.

The reduction of food intake in response to bacteria is posited to be a favourable host reaction. This report attempted to examine whether gastric emptying is involved in the known conditionability of this response. Additionally, this study investigated the role of prostaglandins in the conditioned anorexic response. To investigate this phenomenon, lipopolysaccharide (LPS) (100 micrograms/kg) was used as the unconditioned stimulus, and paired with a novel 1% saccharin solution (conditioned stimulus). Upon conditioned stimulus (CS) representation, experimental animals displayed a marked reduction in food consumption (experiment 1) and emptying of gastric contents (experiment 2). Additionally, treatment with indomethacin upon CS reexposition blocked both the conditioned anorexia and suppression of gastric emptying. These results indicate that conditioned anorexia is possibly the result of a conditioned inhibition of gastric emptying, and this process is mediated by conditioned alterations in PG levels.

Animals↗

Behavioral conditioning of endotoxin-induced plasma iron alterations.

The cascade of physiologic mechanisms in response to infection, the acute-phase response, is recognized as playing a major role in host defence. One such response is the hypoferremia that is consistently reported to occur during bacterial infection. This study aimed to determine whether the alterations in plasma iron were conditionable using the conditioned taste aversion (CTA) paradigm. The regime involved the pairing of a novel-tasting saccharin solution with bacterial endotoxin. Seven days after the initial pairing of these stimuli (the test day), the saccharin solution was represented. Animals exposed to this condition displayed a significant reduction in the level of plasma iron. Animals treated with an intraperitoneal dose of 400 micrograms/Kg lipopolysaccharide (LPS) displayed lower conditioned iron levels than rats infused with 100 micrograms/Kg LPS; however, this difference was not significant. These results showed that in addition to other acute-phase responses (fever and anorexia), plasma iron alterations are able to be manipulated through behavioral manipulations.

Animals↗

Paradoxical conditioning of the plasma copper and corticosterone responses to bacterial endotoxin.

The cascade of physiologic mechanisms in response to infection, the acute phase response, is recognized as having a major role in host defense. Two such responses are an increase in plasma copper and activation of the hypothalamic-pituitary-adrenal axis, which are consistently reported to occur during bacterial infection. We aimed to determine whether the alterations in plasma copper and corticosterone were conditionable using the conditioned taste aversion paradigm. The regime involved the pairing of a novel-tasting saccharine solution (the conditioned stimulus) with lipopolysaccharide (the unconditioned stimulus). Seven days after the initial pairing of these stimuli (the test day), the saccharine solution was represented. Animals exposed to this condition displayed a significant decrease in plasma copper levels. In addition, these rats experienced a reduction in plasma corticosterone that was time dependent. Paradoxically, the conditioned response of both these variables were in a direction contrary to that reported during bacterial infection. These results suggest that some acute phase responses may condition as a rebound response, or in an opposing trend to that occurring as the initial reaction.

Acute-Phase Reaction↗

Acute-phase immune response: lipopolysaccharide-induced fever and sleep alterations are not simultaneously conditionable in the rat during the inactive (light) phase.

Recent research has demonstrated that specific parameters of the immune system can be augmented by behavioral conditioning. These physiological alterations have been largely achieved by implementation of the conditioned taste aversion paradigm. Fever and sleep alterations are early occurrences within the acute-phase immune response to infection. The present study attempted to concurrently condition these two simultaneous, yet independent, responses. Lipopolysaccharide (LPS) was used as an unconditioned stimulus. When paired with a novel-tasting saccharin solution, a conditioned febrile response was observed. However, the somnogenic effects of LPS were not simultaneously conditionable. The conditioning of fever, as well as other interleukin-1-mediated responses, offers promise in both clinical and experimental applications.

Acute-Phase Reaction↗

Inhibition of endotoxin-induced temperature change by behavioral conditioning using alpha-melanocyte-stimulating hormone as an unconditioned stimulus.

The experiments reported here investigate the conditionability, using taste aversion conditioning, of the antagonistic effects of alpha-MSH on the thermoregulatory changes associated with injection of bacterial endotoxin lipopolysaccharide (LPS) in rats. Animals were administered LPS and then given alpha-MSH, as an unconditioned stimulus (UCS), in association with the novel taste of saccharin, the conditioned stimulus (CS). The temperature response at this time in alpha-MSH-treated rats was similar to that observed in control animals. However, 7 days later, when these animals were again injected with LPS but re-exposed to saccharin alone, there was a significant reduction in the temperature response profile compared to controls. These results demonstrate that in male rats the conditioned antipyretic effect following conditioning with alpha-MSH as the UCS is sufficiently robust to counteract the acute effects on body temperature of an LPS injection at the time of CS reexposure. This complements previous experiments demonstrating that thermoregulation may be influenced by cognitive association.

Animals↗

Lithium chloride and immunomodulation in taste aversion conditioning.

Lithium chloride has been used in many studies of conditioning to induce taste aversion behaviour, and in some experiments investigating conditioning effects on immunity it has been used on the assumption that it is immunologically neutral. The studies reported here, however, indicate that LiCl is not immunologically neutral and when used to endow a UCS with noxious properties to enhance the behavioural response in taste aversion conditioned immunosuppression, it may antagonize the residual immunosuppression following initial UCS administration and also the conditioned immunosuppression occurring after CS reexposure. Therefore, conclusions drawn from studies of behaviourally conditioned immunomodulation where LiCl is used as part of either the CS or UCS may require reevaluation.

Animals↗

Modulation of body temperature through taste aversion conditioning.

Injection of rats with bacterial lipopolysaccharide (LPS) results in an initial fall in body temperature followed by a fever. Lithium chloride (LiCl) injection induces a fall in body temperature without subsequent fever production. When these substances were incorporated as unconditioned stimuli in a taste aversion conditioning paradigm, using saccharin flavour as the conditioning stimulus, these differential effects on body temperature were reenlisted on reexposure to saccharin alone 7 days after conditioning. The changes in body temperature on reexposure were similar in direction and kinetics as on the conditioning day although reduced in magnitude. The finding of a true conditioned effect in these studies is in contrast to the paradoxical or compensatory conditioned body temperature responses described elsewhere using different conditioning models. This apparent conflict may be explained on the basis of different unconditioned stimuli acting on efferent versus afferent arms of a negative feedback system. Since body temperature changes often occur in association with immune responses, these findings may have implications to behavioural conditioning of immunity, the outcome of which may reflect the indirect effects on immunity of inadvertent conditioning of thermoregulatory changes.

Animals↗

Alpha-melanocyte-stimulating hormone conditioned suppression of a lipopolysaccharide-induced fever.

Recent investigations have demonstrated the susceptibility of various components of the immune system to behavioral conditioning, using a conditioned taste aversion (CTA) paradigm. In Experiment 1 the effective antipyretic dose (40 micrograms/kg) and duration of antipyretic action (up to 4 hr) of alpha-melanocyte-stimulating hormone (alpha-MSH) was determined in rats tested with lipopolysaccharide (LPS). In the second experiment, alpha-MSH was used as the unconditioned stimulus (UCS) and paired with a novel-tasting saccharin solution (0.1%) to elicit a conditioned antipyretic response to a fever induced one hour previously by LPS. Both the antipyretic effect of alpha-MSH and the pyrogenic effect of LPS were found to be significantly conditionable. The conditioning of fever/antipyretic responses demonstrates for the first time that still another aspect of the host response can be influenced by conditioning procedures.

Animals↗