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16 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1988

The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

conditioned taste aversion↗
NASA NTRS1990

Conditioned taste aversion and motion sickness in cats and squirrel monkeys

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

area postrema↗
NASA NTRS1988

Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

Robert A Fox↗
NASA NTRS1991

Reassessment of area postrema's role in motion sickness and conditioned taste aversion

On the basis of classical studies on the role of the area psotrema (AP) in motion-induced emesis it was generally accepted that the AP is an essential structure for the production of vomiting in response to motion. However, in more recent studies it has been demonstrated that vomiting induced by motion can still occur in animals in which the AP has been destroyed bilaterally. It was inferred from some of these more recent studies that the AP plays no role in motion-induced emesis. From the standpoint of the current understanding of central nervous system (CNS) plasticity, redundancy, remodeling, unmasking, regeneration, and recovery of function, however, it is important to realize the limitations of using ablation procedures to determine the functional role of a given neural structure in a highly integrated, adaptable central nervous system (CNS). For example, the results of our recent investigations in cat and squirrel monkey on the role of the AP in emesis and conditioned taste aversion induced by motion indicate that while AP lesions do not prevent motion-induced emesis when animals are tested 30 days or more after surgery, the lesions do change the latency to emesis. Thus, contradictory findings from lesion studies must be evaluated not only in terms of species difference, differences in lesioning techniques and extent of lesions, and in stimulus parameters, but also in terms of duration of the recovery period, during which significant recovery of function may take place. In our judgment, inadequate consideration of the foregoing factors could lead to erroneous inferences about given structure's role in the behavior of the intact, nonablated animal.

N G Daunton↗
NASA NTRS1990

Investigating motion sickness using the conditioned taste aversion paradigm

The avoidance of foods which are associated with uncomfortable or aversive internal states has long been recognized. Many people are aware, either directly or via anecdotal reports, of individuals who avoid foods which were eaten just before the onset of sickness. Awareness of this phenomenon can be traced to the writings of John Locke. The disruption of diet during cancer therapy is sometimes ascribed to the attribution of an unpleasant quality to foods eaten preceding the sickness induced by therapy itself. In addition, it has long been recognized by the manufacturers of rodent poisons that animals avoid the injection of food treated with nonlethal doses of poison. An important part of the laboratory study of this phenomenon was directed toward studying the role learning plays in this type of avoidance behavior. Following the lead of Garcia and his associates, this avoidance has come to be interpreted as arising from a form of classical conditioning. In typical laboratory studies of this behavior, a novel food is ingested just prior to exposure to some stimulus, commonly poisoning or irradiation, which produces illness. Following the terminology of classical conditioning, it is common to describe this procedure as one of 'pairing' a conditioned stimulus (CS), the novel food, with an unconditioned stimulus (US), the illness induced by toxicosis or irradiation. Avoidance of the food in succeeding feeding opportunities is viewed as a learned response or a conditioned taste aversion (CTA). Garcia et al. asserted that motion sickness could produce 'gustatory' aversions, but passive motion was first reported as an US to establish CTA by Green and Rachlin. The purpose is to review the manner in which CTA has been used to study motion sickness. Numerous reviews concentrating on other aspects of CTA are available in the existing literature. Readers are encouraged to consult the various papers and edited books for extensive information on other aspects of this literature.

Robert A Fox↗
NASA NTRS1984

Area postrema ablations in cats: Evidence for separate neural routes for motion- and xylazine-induced CTA and emesis

The effects of off-vertical rotation upon the Intake of tap water Immediately after rotation, and upon conditioned taste aversion, were assessed In mice with the tilt of the rotation axis varying from 5 to 20° from the earth-vertical. Conditioned taste aversion occurred In all mice that were rotated, but the Intake of tap water was suppressed only In mice that were rotated at 15 or 20° of tilt. The greater suppression of tap water Intake and the stronger conditioned aversion In the mouse as the angle of tilt was Increased In this experiment are consistent with predictions from similar experiments with human subjects where motion sickness develops more rapidly as the angle of tilt la Increased. It was suggested that off-vertical rotation may be a useful procedure for Insuring experimental control over vestibular stimulation In animal studies of motion sickness.

Robert A Fox↗
NASA NTRS2003

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Non-NASA Center↗
NASA NTRS1988

Role of the area postrema in three putative measures of motion sickness in the rat

After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

Richard L Sutton↗
NASA NTRS1991

Relationship of area postrema to three putative measures of motion sickness

Although the rat has an incomplete emetic reflex, several species-specific responses to motion were proposed as measures of 'motion sickness' in rats. The purpose was to determine the dependence of these responses on one of several neural structures known to be essential to motion-induced vomiting in species with a complete emetic reflex. The Area Postrema (AP) was shown to play an important role in the production of motion sickness in vomiting species. The effects of thermo-cautery ablations of the AP on three different responses supposedly reflecting motion sickness in the rat were compared: conditioned taste aversion (CTA); drinking suppression; and fecal boli. Efficacy of the ablations was determined by subjecting ablated, sham-operated, and unoperated control animals to a CTA test which is known to require a functional AP. Animals with AP ablations failed to form CTA when 0.15 M LiCl was paired with a 10 percent sucrose solution, while sham-operated control subjects conditioned as well as the unoperated control subjects. The extent of the ablations was evaluated histologically at the end of the experiment. To determine the effects of the ablations on the measures of motion sickness, all animals were subjected to rotation for 30 min or 90 min on a platform displaced 20 deg from earth horizontal. Results indicate that ablation of AP in the rat has no effect on the formation of CTA to a 4 percent solution of cider paired with motion, on the suppression of drinking immediately after exposure to motion, or on the frequency of fecal boli during exposure to motion. This failure of AP ablations to eliminate the effects of motion on any of these responses discourages their use as equivalents of motion-induced vomiting. The appropriateness of other suggested measures, e.g., pica, remains untested but the dependence of such measures on stimulation more severe than commonly used in motion sickness research and the absence of a demonstration of their dependence on neural structures essential to motion sickness in vomiting species, suggest caution in the use of such responses. Further, until more is known about the neural structures underlying these putative measures, the rat will remain a questionable subject in which to study motion sickness.

R Sutton↗
NASA NTRS2004

The effects of proton exposure on neurochemistry and behavior

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints. Published by Elsevier Ltd on behalf of COSPAR.

Non-NASA Center↗
NASA NTRS1991

Motion sickness elicited by passive rotation in squirrel monkeys

Previous studies on the role of the area postrema (AP) in vomiting induced in the cat by motion and drugs have shown that the AP is not essential for motion-induced vomiting, but is necessary for vomiting to apomorphine and xylazine. To confirm these findings and to determine the role of the AP in the formation of Conditioned Taste Aversion (CTA), the AP was ablated bilaterally in 10 adult female cats. With one exception, the ablated cats continued to vomit to the same 1n0tion that elicited emesis before the ablation. Doses of xylazine and apomorphine that elicit emesis in intact cats, failed to induce emesis in the ablated cats. Histological examination indicated that 8 cats had complete lesions and 2 had partial lesions. Investigations of effects of AP ablations on CTA revealed that cats with complete lesions did not form CTA to flavored milk paired with xylazine injections. However, cats with partial lesion developed xylazine-induced CTA. Seven of the 8 completely lesioned cats developed motion-induced CTA, even though emesis was not consistently elicited by motion. These results suggest that there are multiple routes for inducing CTA and the emetic reflex, that CTA can form without eliciting emesis, and that CTA may be a sensitive measure of sub-emetic motion sickness.

M Corcoran↗
NASA NTRS0992

Current status: Animal models of nausea

The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

Robert A Fox↗
NASA NTRS1998

Effects of exposure to different types of radiation on behaviors mediated by peripheral or central systems

The effects of exposure to ionizing radiation on behavior may result from effects on peripheral or on central systems. For behavioral endpoints that are mediated by peripheral systems (e.g., radiation-induced conditioned taste aversion or vomiting), the behavioral effects of exposure to heavy particles (56Fe, 600 MeV/n) are qualitatively similar to the effects of exposure to gamma radiation (60Co) and to fission spectrum neutrons. For these endpoints, the only differences between the different types of radiation are in terms of relative behavioral effectiveness. For behavioral endpoints that are mediated by central systems (e.g., amphetamine-induced taste aversion learning), the effects of exposure to 56Fe particles are not seen following exposure to lower LET gamma rays or fission spectrum neutrons. These results indicate that the effects of exposure to heavy particles on behavioral endpoints cannot necessarily be extrapolated from studies using gamma rays, but require the use of heavy particles.

NASA Discipline Radiation Health↗
NASA NTRS1999

Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

Poloxamer/pharmacology↗
NASA NTRS2000

Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS2004

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Review↗