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Biomedical subjects

T L Davidson

Publications and source records attributed to T L Davidson.

At least 37 records · Page 2Linked to original sources

Design of an airborne plutonium survey program for personnel protection.

Various options were considered for surveying and real-time monitoring for airborne plutonium for optimum protection of personnel. Placement of samplers, dilution factors, and analysis time were considered in the strategy for achieving regulatory compliance and maintaining internal dose as low as reasonably achievable (ALARA). It was found that protection was relatively insensitive to placement as was sensitivity of detection. It was also found that maximum protection was obtained with few detectors and increasing the number of detectors above the optimum value did not appreciably increase the information about a release nor did it aid in locating the release. It was determined that the best protection was obtained with alarming monitors if the detection sensitivity was sufficiently low. Integrating samplers requiring laboratory analysis can be more sensitive than alarming monitors, but the lack of timeliness limits the amount of protection. The integrating samplers can be used effectively to monitor engineering controls. Personal air samplers also offer little protection but can be very effective in analyzing exposure by craft and job type.

Air Pollutants, Radioactive↗

Arousal response from sleep to tracheal obstruction in lambs during postnatal maturation.

Experiments were carried out to investigate the arousal response from sleep to tracheal obstruction in lambs during postnatal maturation. Ten fetal sheep were instrumented with electrodes for sleep staging and a tracheotomy was done. After spontaneous vaginal delivery, serial experiments were carried out on the lambs at five postnatal ages: 18-48 h and 4, 6, 11, and 18 d. During an experiment, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that tracheal obstruction could be produced by inflating the balloon. Measurements were made in quiet sleep and active sleep during control periods of tidal respiration and during experimental periods of tracheal obstruction. Neither sleep state nor age influenced control arterial Hb oxygen saturation (SaO2). SaO2 decreased significantly before arousal during tracheal obstruction in quiet sleep at 18-48 h and in active sleep at all ages. The SaO2 at arousal was always lower in active sleep than in quiet sleep. Overall, however, there were no significant effects of age on the change in SaO2 before arousal in either quiet sleep or active sleep. The time to arousal during tracheal obstruction increased between 18-48 h and 6 d of postnatal life in active sleep but not in quite sleep. Our data provide evidence that the arousal response to tracheal obstruction is functional by 18 h of postnatal life in lambs. The increase in time to arousal after tracheal obstruction in active sleep most likely results from state-specific changes in the factors governing oxygen supply and demand.

Aging↗

Cholecystokinin, but not bombesin, has interoceptive sensory consequences like 1-h food deprivation.

A comparison of the interoceptive sensory consequences of cholecystokinin, bombesin, and 1-h food deprivation was conducted in rats. In two experiments, rats were first trained to use stimuli arising from different degrees of food deprivation (1 and 24 h or 1 and 4 h) as discriminative signals for shock, and were then tested for generalized control of discriminative responding (i.e., conditioned freezing) by cues arising from injection of 4 micrograms/kg (Experiment 1 only) and 8 micrograms/kg cholecystokinin (Experiment 1A only), 12 micrograms/kg bombesin (BBS), and isotonic saline, respectively. The effects of these peptides on food intake were also assessed. In both experiments, BBS and cholecystokinin (CCK) each suppressed feeding relative to saline; however, generalization of discriminative responding was obtained only following CCK. Generalization depended on prior learning about food deprivation cues--CCK had little effect on freezing in rats that showed weak discrimination performance (i.e., rats trained with 1- and 4-h deprivation cues). The results indicated that CCK but not BBS produces interoceptive cues like those occurring under 1-h food deprivation.

Animals↗

A role for hippocampus in the utilization of hunger signals.

The hippocampus is generally regarded as an important anatomical substrate for learning and memory (e.g., Eichenbaum, Otto, & Cohen, Behavioral and Neural Biology, 57, 2-36, 1992; Squire, Psychological Review, 99, 195-231, 1992). In the present research, we provide evidence that the hippocampus is also involved with another function--utilization of hunger state signals. Rats with selective ibotenate lesions of the hippocampus were found to be impaired in their ability to discriminate between the interoceptive sensory consequences of food deprivation and satiation. At the same time the ability of these rats to discriminate between different exteroceptive cues was unaffected. These results suggest that deficits in discriminative performance were specific to interoceptive state stimuli. In addition, hippocampal-damaged rats also seemed unable to use their food deprivation stimuli as signals to engage in normal feeding behavior. Our results argue that although the hippocampus may be important for learning and memory processes, it also deserves consideration as a neural substrate for the regulation of food intake and perhaps other functions which involve interoceptive signals.

Animals↗

Hippocampal lesions do not impair negative patterning: a challenge to configural association theory.

According to configural association (CAS) theory (Sutherland & Rudy, 1989), an intact hippocampus is required for rats to solve learning problems that are based on "configural" processes. This theory identifies the negative patterning discrimination as a critical example of this type of problem. Rudy and Sutherland (1989) reported disruption of negative patterning following hippocampal formation damage produced by intracranial infusion of a mixture of kainic acid + colchicine (KA + COL). We assessed acquisition of negative patterning in rats with hippocampal damage produced by KA + COL compared with rats with more selective ibotenate lesions of hippocampus. Neither group showed impaired negative patterning relative to controls. A transfer test provided evidence that all groups used configural processes to solve the problem. Thus contrary to CAS theory, the hippocampus is not an important substrate for the operation of configural processes.

Acoustic Stimulation↗

The nature and function of interoceptive signals to feed: toward integration of physiological and learning perspectives.

The idea that different states of energy need give rise to distinct interoceptive sensations has been basic to many accounts of the physiological and the learned controls of feeding. Yet, a number of difficulties have complicated attempts to provide direct evidence for this view. The present article describes a research strategy that confirms that food deprivation states produce salient interoceptive stimuli in rats. The implications of this research for the physiological origins of energy state signals, the brain structures involved with processing energy state information, and the manner in which signals of energy need influence feeding were considered. The possibility that food deprivation cues influence feeding by modulating the activation of associations involving external events and their postingestive aftereffects was discussed with reference to earlier associative accounts of the function of hunger signals.

Animals↗

Cl- replacement alters the ventilatory response to central chemoreceptor stimulation.

To determine whether cerebrospinal fluid (CSF) Cl- has a role in determining the stimulus to the central respiratory chemoreceptors under conditions of constant CSF pH, CO2, and HCO3- concentrations, the ventral medullary surface of the anesthetized rat was perfused with mock CSF of various ion composition and pH. Four mock CSF perfusates were used: two normal pH control perfusions and two acidic solutions. One acidic perfusate was formulated in the traditional manner by substituting Cl- for HCO3-. The second acidic perfusate, and one of the normal pH control perfusates, had approximately 15% of the Cl- replaced with isethionate, an impermeant strong anion. When the two acidic solutions were perfused over the ventral medulla, consistently larger increases in both tidal volume and minute ventilation were observed with the isethionate-containing acidic solution, despite conditions of identical pH and PCO2. The unequal ventilatory effects of the two acidic perfusions suggest that Cl- transport may be a factor determining the stimulus to the central respiratory chemoreceptors.

Animals↗

Ontogeny of a circadian rhythm in body temperature in newborn lambs reared independently of maternal time cues.

To investigate the ontogeny of a circadian rhythm in body temperature, we performed 24-h temperature measurements at six postnatal ages in ten newborn lambs reared independently of their ewes. At 18 to 48 h of age, a significant time-of-day variation in body temperature was found, the variation achieving a peak between 5.00 pm and 6.00 pm. Over the next two weeks, this time-of-day variation disappeared, reappearing at 18 days of age, although the phase had shifted such that the peak temperature was achieved between 8.00 am and 9.00 am. At 26 days of age, the time-of-day variation in body temperature was still present, maintaining the same phase relationship as at 18 days of age. It is possible that the significant time-of-day variation observed in the two oldest groups is due to the emergence of a discernable circadian rhythm in body temperature entrained to the light-dark cycle during the second or third week of life, whereas the time-of-day variation observed in the 18 to 48-h old is due to residual effects of entrainment to maternal zeitgebers. We speculate that the lack of any observable time-of-day variation in the 4, 6 and 11 days-old lambs may denote the presence of no rhythm or possibly a free-running rhythm in body temperature in subjects not yet able to entrain to photic zeitgebers.

Animals↗

Development of tolerance to endogenous opiates activated by 24-h food deprivation.

Four experiments assessed the effects of exposure to 24-h food deprivation on the tail-flick latency of rats exposed to a temperature stimulus. Confirming previous studies, Experiment 1 showed that food deprivation gave rise to analgesia, as indicated by increased tail-flick latencies, that was antagonized by naloxone. Experiment 2 found that analgesia was greatly reduced after five exposures to periods of 24-h food deprivation (alternating with 24-h free access to food), indicating the development of tolerance. Experiments 3 and 3a examined the development of tolerance to the analgesic effects of morphine following repeated morphine injections, saline injections, and exposure to 24-h food deprivation plus saline injections. The combined results of both experiments provided evidence that repeated exposures to either morphine or food deprivation, produced greater tolerance to morphine than did exposures to saline. That food deprivation was cross-tolerant with morphine indicated that tolerance to food deprivation-induced analgesia involved opioid mechanisms. The relevance of opioid tolerance to psychobiological models of feeding and to the development of an animal model of anorexia nervosa was discussed.

Analgesia↗

Potency of food deprivation intensity cues as discriminative stimuli.

Rats were trained to use stimuli arising from 0 and 24 hr without food as discriminative signals for shock. In Experiment 1, one group was shocked under 0-hr food deprivation and not shocked under 24-hr food deprivation. Another group received the reverse contingency. The groups received only 3 training trials under each deprivation level. Learning was revealed in a test phase when greater extinction of freezing was observed under the nonshocked than under the shocked deprivation level for both groups. A similar pattern of results was obtained in Experiment 2 when auditory cues were also relevant throughout training. Furthermore, prior training with food deprivation cues seemed to reduce learning about auditory cues subsequently trained in compound with deprivation stimuli. The results indicate that food deprivation intensity cues can be potent discriminative stimuli. The idea that deprivation cues function as conditioned modulatory stimuli cues is also discussed.

Animals↗

On the hippocampus and learned conditional responding: effects of aspiration versus ibotenate lesions.

To study the possible involvement of the hippocampus in learned conditional responding, rats with aspiration lesions of the hippocampus and others that had the hippocampus removed with ibotenic acid were trained on concurrent Pavlovian conditional and nonconditional discriminations. In agreement with the results reported by Ross et al. (1984), animals that had the hippocampus removed with aspiration were unable to learn the conditional discrimination, but learned the simple nonconditional discrimination without difficulty. In contrast, rats that had the hippocampus removed with ibotenic acid did not differ from controls in learning either discrimination. Furthermore, transfer test results were consistent with the hypothesis that ibotenate-lesioned rats performed conditional operations to solve the conditional discrimination problem. Histological analysis indicated that the ibotenate lesions resulted in the removal of the hippocampus and dentate gyrus with minimal involvement of other structures. In aspiration hippocampal animals there was less overall damage to the hippocampus, but there was also extensive damage to the axons passing in alveus and fimbria, together with bilateral loss of cells in the subicular complex, the cingulate gyrus, and the cortex. Since rats with ibotenate lesions had more complete removal of the hippocampus, yet learned both discriminations, the impaired conditional responding found in aspiration hippocampals must be due to extrahippocampal damage.

Animals↗

Conditioned reversal of reactions to normally avoided tastes.

Oral motor responses, elicited by the infusion of a taste solution into a rat's mouth, can be changed through association with either other tastes or internal states. Such changes have been well established when ingestive responses, elicited by a normally preferred taste, are changed to aversive responses when the taste signals a LiCl injection. However, the converse has yet to be clearly established; that aversive responses, elicited by a normally avoided taste, can be changed to ingestive responses in a nondeprived animal, as a result of conditioning. We demonstrate here that when a normally avoided taste (quinine or HCl) signals a preferred taste (sucrose), the oral motor responses gradually undergo two types of change as a function of trials. The aversive oral motor responses elicited by the avoided taste decrease over trials and the ingestive responses increase. The two measures, ingestive and aversive responding, were obtained by recording the rat's reactions to the stimuli as they were infused directly into the oral cavity. This taste reactivity method both enabled us to use avoided stimuli in a nondeprived animal and to measure the rat's evaluation of the stimuli's aversiveness. Problems with stimulus sampling may be responsible for the dearth of conditioning experiments which utilize avoided tastes in conditioned preference studies.

Animals↗

Discontinuation of diazepam and sensitivity to a shock signal: fear conditioning prior to drug treatment.

The present experiment examined the disruptive capacity of a shock CS when Pavlovian training was completed prior to repeated daily treatment with diazepam (DZ). Two groups of rats were given 20 Pavlovian fear conditioning trials (two per day) to establish a light CS as a shock signal. Both groups were then trained for 15 daily sessions to bar press for food reinforcement. Before each session, one group was injected IP with 5 mg/kg DZ and the other with saline. All injections were discontinued after the last training session. Nine days later, the capacity of the CS to disrupt bar pressing was tested. The CS produced greater disruption of bar pressing for rats that had previously received chronic diazepam treatment. The results suggest that DZ discontinuation increases sensitivity to cues established as fear elicitors prior to initial administration of DZ.

Animals↗

The long-term effects of diazepam, lorazepam, and buspirone on behavioral suppression by a shock signal.

1. Two experiments examined the long-term effects of treatment with buspirone (a nonbenzodiazepine anxiolytic), diazepam, or Lorazepam (two pharmacokinetically distinct benzodiazepines) on the capacity of a shock cue to disrupt appetitively conditioned behavior. 2. In Experiment 1, rats were injected with diazepam (5 mg/kg), buspirone (1.5 mg/kg or .75 mg/kg), or saline shortly before each of 12 bar press training sessions. Injections were suspended and three days later the rats received five days of Pavlovian fear conditioning (bars removed) in which a tone signaled shock. The capacity of the tone to disrupt bar pressing was then assessed. 3. Bar pressing of rats previously injected with diazepam was more suppressed by the shock cue than that of rats previously injected with buspirone or saline. The long-term effects of buspirone and saline did not differ. 4. In Experiment 2, Lorazepam had effects different from diazepam during bar press training. Nonetheless, rats previously injected with Lorazepam were also more disrupted by a shock cue than were controls. 5. The results suggest that one long-term consequence of treatment with benzodiazepines may be hypersensitivity to behavioral disruption by stimuli that presumably elicit fear or anxiety.

Animals↗

An animal model to detect the neuropsychological toxicity of anticancer agents.

The unexpected discovery that certain chemotherapeutic agents used in the treatment of childhood cancers have neurocognitive side effects has prompted a search for techniques that identify those medications that place children at risk. An animal model for the assessment of resultant neurocognitive toxicity is described which makes use of simple classical conditioning. We have shown that rats learn about environmental events more slowly following neonatal administration of methotrexate. The changes after methotrexate exposure are not related to stimulus characteristics or to perceptual abilities, but rather to damage to the neural systems involved in acquisition, retention, or recall. Similar problems with learning have been observed in children treated with methotrexate. An effective animal model such as the one described here may help detect and avoid antineoplastic agents that produce severe cognitive defects in childhood cancer patients.

Animals↗

Comparison of the interoceptive sensory consequences of CCK, LiCl, and satiety in rats.

In three experiments we assessed the degree to which ad lib feeding, injection of cholecystokinin (CCK), and injection of lithium chloride (LiCl) produce states with similar sensory consequences. In each experiment, two groups of rats were trained to use cues arising from food deprivation and satiation as discriminative signals for shock. One group was shocked when deprived but not when nondeprived. The other group received the reversed discrimination. Testing began when incidence of freezing was greater under the shocked deprivation than under the nonshocked deprivation condition. In Experiment 1, the rats were tested under 24-hr food deprivation after injections of CCK, LiCl, and saline (in counterbalanced order). We reasoned that if either CCK or LiCl induce satiety-like states, they should promote patterns of responding different from those produced by saline but similar to those produced by ad lib feeding. The effects of CCK on freezing did not differ from those of saline, whereas both CCK and LiCl had effects that were different from ad lib feeding. This pattern of results was also obtained when deprivation level during training and testing was reduced to 8 hr (Experiment 1A) and also when rats received small amounts of food in conjunction with CCK (Experiment 2). The intubation of a high-calorie stomach load (Experiment 1A) produced a response profile like that observed after free feeding. Freezing after LiCl treatment differed from that observed after free feeding and from that found after injection of CCK. The results indicate that rats can differentiate between the sensory consequences of the states produced by CCK, by LiCl, and by ad lib feeding.

Animals↗

Long-term effects of yohimbine on behavioral sensitivity to a stressor.

Two experiments examined the long-term effects of repeated administration of yohimbine, a suspected anxiogenic drug, on behavioral sensitivity to a conditioned cue for shock. In Experiment 1, rats were trained to bar press following injection of yohimbine (either 1 or 2 mg/kg) or saline. At the end of this training, injections were suspended and the rats were given Pavlovian fear conditioning to establish a light as a shock signal. Rats were then returned to the bar press situation (about 2 weeks after their last injection) and the capacity of the light to disrupt responding was tested. Rats previously treated with yohimbine were less disrupted by the light than were controls. In contrast, Experiment 2 found that previously experiencing the yohimbine-induced state only in the home cage increased subsequent disruption of bar pressing by the light. Yohimbine pretreatment had no effect on acquisition of freezing behavior to the light, nor on bar pressing during testing in the absence of the light, in either experiment. The results show that yohimbine can have long-term effects on behavior in the presence of a stressor, and that the nature of these effects are dependent upon environmental and/or behavioral context in which the yohimbine-induced state was experienced. These findings appear compatible with an internal stimulus view of stress and stress inoculation.

Animals↗