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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1984

The Structure of the Mammalian Area Postrema

The area postrema in mammals other than rodents and lagomorphs is a bilateral mound of gelatinous-appearing tissue that protrudes into the caudal fourth ventricle on either side of the obex. In rodents and lagomorphs it is a single midline structure at the apex of the calamus scriptorius. The vasculature is derived mainly from the posterior inferior cerebellar arteries and consists mainly of sinusoidal capillaries. It appears to constitute a portal system, at least in the rat. Many of the capillaries are fenestrated, and many large perivascular spaces with both vascular and parenchymal basal laminae are present. The cell population is composed of flattened ependymal cells exhibiting microvilli, and of small neurons, normal astrocytes, glialoid cells, and a very few oligodendroglia. Mast cells are occasionally present. The glialoid cells appear to be the predominant cell type and exhibit great numbers of vascular podia. Axodendritic synapses are numerous and axosomatic synapses are occasionally seen in the parenchyma. Synaptic vesicles are mainly of the clear-cored type but large dense-cored vesicles are commonly observed in some axon terminals.

Brizzee, K. R.↗
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 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 NTRS1986

Axoglial contacts in the area postrema of the cat - An ultrastructural study

Axoglial contacts were observed in an ultrastructural study of the area postrema of the cat. According to the disposition of the electron-dense projections attached to the adjoining membranes these contacts were classified as symmetrical or asymmetrical. The axon profiles contained aggregations of clear vesicles randomly distributed or grouped in clusters adjacent to the electron-dense projections. Dense core vesicles were occasionally seen. The neuroglial profiles were either astrocytic or ependymoglial in nature. The astrocytes showed a clear cytoplasm, polymorphous vesicles, mitochondria, glycogen granules, and bundles of filaments. The ependymal cells, in contrast, had a more electron-dense and granular appearance, tubular structures, irregular vesicular formations, profiles of smooth reticuloendoplasm, and filaments grouped in bundles or isolated in the cytoplasm. The possibility that these contacts might play a role in the chemical transfer from neurons to glial cells is discussed on the basis of existing biochemical data.

Damelio, Fernando E.↗
NASA NTRS1985

Immunocytochemical localization of glial fibrillary acidic protein (GFAP) in the area postrema of the cat - Light and electron microscopic study

Glial fibrillary acidic protein (GFAP) was demonstrated in the cytoplasm and processes of ependymal cells and astroglial components of the area postrema of the cat. These observations differ from the findings in the ependyma of the ventricular cavities which are consistently negative for the protein. Since some studies have suggested sensory functions of the glial cells in this emetic chemoreceptor trigger zone, a careful consideration of morphological and biochemical attributes of these cells seems appropriate.

Damelio, F. E.↗
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 NTRS1980

Effect of Ablation of Area Postrema on Frequency and Latency of Motion Sickness-Induced Emesis in the Squirrel Monkey

Twelve young adult squirrel monkeys of the Bolivian subspecies were subjected to continuous counter-clockwise horizontal rotary motion at 25 rpm, together with a sinusoidal vertical excursion of 6 in. every 2 sec (0.5 Hz). Each animal was exposed to this motion regimen for a period of 60 min once each week for three consecutive weeks. Following the third weekly motion test bilateral ablation of the Area Postrema (AP) was performed in eight of the animals by thermal cautery. Two control animals were sham-operated after the third motion test while two additional controls were given the motion tests as noted above but were not operated. The four controls were considered as a single group for statistical analyses of results of the motion tests. After a recovery period of 30 to 40 days, and at a comparable interval in the non-operated controls, each animal was again tested for motion sensitivity for three consecutive weeks. The brains of all of the animals were then fixed by left ventriculal cardiac perfusion with Bouin's fluid and processed for histological evaluation of the bilateral AP ablation in comparison with the control brains. Five of the AP-ablated animals postoperatively were completely refractory to the motion stimuli, two exhibited a decreased number of emetic responses, and one exhibited the same number of responses before and after the AP lesions. The controls exhibited no significant difference in emetic sensitivity on the second series of three weekly tests than on the first series. The results of this investigation appear to be in agreement with the observations of Wang and Chinn in the dog indicating that the integrity of the AP (CTZ) is essential to the emetic response to motion.

Brizzee, K. R.↗
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 NTRS1991

Recovery of the vomiting reflex following area postrema ablation in squirrel monkeys

Current theory and recent evidence suggest that motion sickness occurs under conditions of sensory input in which the normal motor programs for producing eye, head, and body movements are not functionally effective, i.e. under conditions in which there are difficulties in maintaining posture and controlling eye movements. Conditions involving conflicting or inconsistent visual-vestibular (VV) simulation should thus result in greater sickness rates since the existing motor programs do not produce effective control of eye-head-body movements under such conditions. We feel that the relationship of postural control to motion sickness is an important one and one often overlooked. We reported the results of a study which showed that when postural requirements were minimized by fully restraining squirrel monkeys during hypogravity parabolic flight, no animals became motion sick, but over 80% of the same 11 animals became sick if they were unrestrained and maintained control of their posture.

Nancy G Daunton↗
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 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 NTRS1987

Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

F Damelio↗
NASA NTRS1988

Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

GABA↗
NASA NTRS1986

Xylazine emesis, yohimbine and motion sickness susceptibility in the cat

The possible role of the alpha-2 adrenoceptors in xylazine-induced vomiting and in motion sickness was investigated. Cats were divided into two groups according to motion sickness susceptibility and were observed after s.c. injections of xylazine. The incidence of vomiting increased with the dose, and at each dose the high susceptibility group had a greater emetic incidence than the low susceptibility group. In another experiment with cats divided into two groups according to motion sickness susceptibility, s.c. administration of yohimbine effectively antagonized the xylazine-induced emesis in both susceptibility groups. The cats in the latter experiment were then challenged with a motion sickness stimulus after s.c. pretreatment with yohimbine. Yohimbine failed to prevent motion sickness but did occasion an unexplained variability in the incidence of vomiting. These findings suggest that the emetic effect of xylazine results from stimulation of alpha-2 adrenoceptors but that these receptors are not fundamental to feline motion sickness. The fact that susceptibilities to xylazine-induced emesis and to motion sickness are correlated suggests a point of interaction other than the area postrema, which is known to be essential for xylazine-induced vomiting but not for motion sickness in the cat.

Lucot, James B.↗
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 NTRS1992

Neural Connectivity and Immunocytochemical Studies of Anatomical Sites Related to Nauseogenic and Emetic Reflexes

The studies conducted in this research project examined several aspects of neuroanatomical structures and neurochemical processes related to motion sickness in animal models. A principle objective of these studies was to investigate neurochemical changes in the central nervous system that are related to motion sickness with the objective of defining neural mechanisms important to this malady. For purposes of exposition, the studies and research finding have been classified into five categories. These are: immunoreactivity in the brainstem, vasopressin effects, lesion studies of area postrema, role of the vagus nerve, and central nervous system structure related to adaptation to microgravity.

Fox, Robert A.↗