Mechanics of vomiting: a minireview.

In a cineradiographic analysis of the vomiting reflex in response to i.v. administration of an emetic drug (lanatoside C, 12 mg/kg) in cats, it was shown that the vomiting act is preceded by cyclic periods of abnormal peristaltic activity of the small bowel and inhibition of gastric peristalsis. It was further observed that massive antiperistalsis of the upper small bowel with reflux into the stomach is a common occurrence in the period immediately preceding vomiting. The emetic act itself is composed of phases of esophageal dilation, gastric emptying, gastric reflux, and esophageal collapse in cyclic repetition. The response of the esophagus and the stomach during emesis is passive, with external pressures and forces apparently providing the expulsive forces, the gastric bolus being contained by contraction of the pylorus and probably an upper esophageal or pharyngeal barrier. Earlier studies were conducted in cats in which observations were made on changes in thoracic venous pressure, abdominal venous pressure, and arterial blood pressure associated with vomiting induced by Veratrum alkaloids. Retching was characterized by a growing series of brief negative intrathoracic pressure pulses mirrored by positive pressure pulses in the abdomen. Expulsion then occurred and was followed with a sudden reversal of intrathoracic pressure from negative to positive. Expulsion involved a more sustained abdominal contraction, but both retching and expulsion were brought about by the same set of muscles, according to their EMG profiles. From results observed following phrenicotomy and spinal cord section at T5, it was concluded that the diaphragm, acting together with the inspiratory muscles against a closed glotis is responsible for the negative intrathoracic pressure that occurs in retching.(ABSTRACT TRUNCATED AT 250 WORDS)

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 was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced 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.

The effect of area postrema lesions on hemodynamic responses to systemic methionine-enkephalin in conscious dogs.

In the intact conscious dog, intravenous methionine-enkephalin (ME) increases heart rate and mean arterial blood pressure (MAP). These hemodynamic responses are produced at lower dosages when ME is injected into the vertebral artery, but not the carotid artery, suggesting that ME receptors are localized in the vertebrobasilar artery circulation. The area postrema (AP), a circumventricular organ devoid of a functional blood-brain barrier, represents a likely site for these receptors. We have tested the effects of chronic AP ablation upon hemodynamic responses to ME in conscious dogs. In three dogs with subtotal AP destruction, ME responses were preserved. However, in another dog with complete ablation of both the AP and the area subpostrema, ME responses were eliminated. These results indicate that total destruction of the AP, and perhaps of deeper structures as well, is necessary to abolish hemodynamic responses to ME.

Neurons numbers and dendritic extent in normal aging and Alzheimer's disease.

Evidence is reviewed regarding neuron numbers and dendritic extent in normal aging in rodent, monkey and human brain and in Alzheimer's disease (AD) in man. Neuron loss and change in dendritic extent appear to be regionally specific but not identical in rodents and primates. In AD there is excess neuron loss and dendritic regression in some but not all brain regions. Overlap between AD and control groups, however, is known to occur. Methods to assess dynamic morphology of the living brain may be superior to analysis of static, post-mortem brain structure in explaining functional deficits in AD and normal aging.

The anti-emetic properties of 1-sulpiride in a ground-based model of space motion sickness.

L-sulpiride, at a dose of 4 mg/kg, essentially abolished motion-induced emesis in a group of 6 squirrel monkeys undergoing horizontal rotation at 25 rpm, a terrestrial model of space motion sickness (SMS). Extrapyramidal side effects were not observed. In the absence of the drug, the usual emetic response returned. In comparison while typical neuroleptics were also strongly anti-emetic, they produced a considerable degree of rigidity and akinesia.

Local brainstem glucose utilization in the squirrel monkey.

The 2-deoxy-D-[14C]-glucose method for the measurement of local cerebral glucose utilization (LCGU) in individual brain nuclei and regions has been applied to the squirrel monkey (Saimiri sciureus). The determinations were conducted in five conscious, lightly restrained adult, female, Colombian squirrel monkeys. Local glucose utilization in brainstem structures (LBGU) was highest in nuclei involved in auditory and vestibular functions and in some nuclei involved in general motor activity. The values for glucose utilization (mumoles/100 g/min) were generally lower than in comparable structures reported by other authors in the rat and slightly lower than those in the macaque monkey. In the Beagle dog the values for "medulla" are markedly lower than for most individual structures in the squirrel monkey medulla, about equal in the inferior colliculus and appreciably higher in the superior colliculus.

Effect of macular ablation on frequency and latency of motion-induced emesis in the squirrel monkey.

Three previously motion-emetic sensitive squirrel monkeys were rendered refractory to a standard motion-emetic regimen by a two-stage utriculosacculectomy procedure which preserved the cristae ampullares of semicircular canals. Three non-operated control squirrel monkeys tested on the same motion-emetic regimen time schedule as the operated animals remained motion-emetic sensitive with regard to incidence, frequency, and latency of motion-induced emetic responses. Following a sham surgical procedure (stapedectomy) performed on two of the latter animals and one additional new animal, the emetic incidence decreased from 100% to 89%, but the frequency and latency were not altered significantly.

Lipofuscin in retinal pigment epithelium of rhesus monkey: lack of diminution with centrophenoxine treatment.

An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sections from the perifovea of ten rhesus monkeys, all approximately 20 years of age. Four of the animals received 80 mg/kg Centrophenoxine (IM injection) daily for 12 weeks. No significant difference between the treated and control groups could be demonstrated statistically (Mann-Whitney U-test) either in the fraction of RPE cell cytoplasm occupied by lipofuscin granules or in the average size of the granules.

Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis.

Central cholinergic pathways modulate both the perception of excessive motion stimuli and the expression of motion sickness symptoms, such as nausea and vomiting. Specific brainstem areas which mediate motion-induced emesis include the area postrema (AP), vagal nuclear complex (VNC), reticular formation (RF) at the site of the vomiting center, and the vestibular complex (VC). In this report, histological studies indicated the cellular organization of brainstem structures mediating emesis was similar in bovine and squirrel monkey brain. The objective of this study was to characterize biochemical and pharmacological properties of muscarinic cholinergic receptors assayed by 3H-QNB binding in these regions of bovine brainstem. Scatchard analyses of specific 3H-QNB binding showed an uneven distribution of muscarinic receptors, with high densities of sites in VNC and AP, intermediate levels in RF and lowest receptor concentrations in VC. Dissociation constants for 3H-QNB, measured in saturation and kinetic experiments, were similar in all brainstem regions. The pharmacological potency of cholinergic agonists and antagonists was the same as reported for muscarinic receptors labeled in other brain areas or peripheral organs. Several drugs which potently inhibited 3H-QNB binding in bovine brainstem also exhibited antiemetic activity in a squirrel monkey model of motion-induced emesis. The antimotion sickness effects of these drugs may be due, in part, to their antagonism of muscarinic receptors in brainstem areas regulating emesis.

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.

Motion-induced alterations in 2-deoxyglucose uptake in brainstem nuclei of squirrel monkeys: autoradiographic and liquid scintillation studies.

Each of 8 young adult female squirrel monkeys were injected via a femoral vein cannula with 167 microCi/100 g body weight of 2-(1,2-3H)-deoxy-D-glucose (2-DG) (New England Nuclear, 37.3 Ci/mmol) in 0.5 ml sterile saline. 4 additional female squirrel monkeys were injected in the same manner with 100 microCi/100 g body weight of the (3H)-2-DG. 2 h after this initial injection the original 8 animals were injected with 16.7 microCi/100 g body weight of 2-(1-14C)-deoxy-D-glucose (51.3 mCi/mmol) in 0.5 ml sterile saline. The 4 additional animals were injected with 25 microCi/100 g body weight of the (14C)-2-DG. Half of the animals each dose level were restrained in the upright position with Velcro straps and a nontraumatic moulded plastic head holder on a modified animal restraint board [Withrow and Devine, 1972] with the head in the sagittal plane but tilted forward about 20 degrees. They were then subjected to horizontal rotary motion at 25 rpm together with a vertical movement of 6 inches at 0.5 Hz for 1 h in a lighted room. The other half of the animals at each dose were restrained in the same manner and maintained in a quiescent state. At the end of this period each animal was anesthetized with ketamine, and the brain was quickly dissected out and frozen in isopentane cooled to -60 degrees C with dry ice. Transverse cryostat sections (-15 degrees C) of the brainstem were cut alternately at 200 and 20 microns from the nucleus gracilis caudally through the superior vestibular nucleus rostrally. Micropunch samples of the individual vestibular nuclei, and other brainstem nuclei and areas were obtained from the 200-microns sections with a modification of the method of Eik-Nes and Brizzee with a small stainless steel punch measuring 850 microns in diameter. The frozen punch samples were prepared for liquid scintillation counting (Beckman LS7500 system). Differential (3H) and (14C) counts (cpm) were made employing external standards. The 20-microns sections were prepared for 14C autoradiography by standard methods employing Kodak SB-5 X-ray film. The (14C) autoradiographs from the motion-stimulated animals revealed a selectively high uptake of 2-DG in all of the vestibular nuclei, the lateral cuneate nucleus and the lateral reticular nucleus as compared with the corresponding structures in the control animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of prenatal ionizing radiation on the visual cortex and hippocampus of newborn squirrel monkeys.

Five squirrel monkeys were exposed to 200 rads whole-body ionizing irradiation (60Co) at 0.4 rads per second on approximately the seventy-fifth day of gestation, and six squirrel monkeys were sham-irradiated. The mean cortical depth and the mean number of neurons per mm3 in the visual cortex was less in irradiated animals than in controls, but the differences were not statistically significant. The mean number of glial cells in this cortical region was significantly lower in the irradiated animals. An analysis of variance of the combined spine count data from apical, basal, and oblique dendrites revealed a significantly lower number of dendritic spines on basal dendrites in irradiated than in control animals in Meynert neurons in the visual cortex of irradiated offspring. In the hippocampus, the depth of the stratum oriens and the combined depth of the strata radiatum, lacunosum, and moleculare were significantly less in irradiated than in control animals, although the difference in the depth of the pyramidal layer, considered individually, was not statistically significant. The mediolateral width of the CA-1, CA-2, and CA-3 zones, as seen in transverse section, was significantly less in irradiated animals than in controls. The number of dendritic spines per unit length of pyramidal cell dendrite in the CA-1 zone and the total number of pyramidal neurons in the CA-1, Ca-2 and CA-3 zones, per transverse section, were significantly lower in irradiated than in control brains. Canonical correlations provided statistical evidence for greater radiation vulnerability of the hippocampus compared to motor and visual areas of the cerebral cortex.

Motion sickness in the squirrel monkey.

Because it is of the same taxonomic order as man, the squirrel monkey has been introduced as a nonhuman primate model for the study of such aspects of motion and space sickness as susceptibility, prevention, treatment, and neural mechanisms. In this study on susceptibility, the specific aims were to examine the effects of combined vertical rotation and horizontal acceleration, phenotype, sex, visual cues, morning and afternoon testing, and repeated test exposures on incidence, frequency, and latency of emetic responses. The highest emetic incidence of 89%, with an emetic frequency of 2.0, during 60 min, and a latency of 19 min from onset of testing, occurred at 25 rpm and 0.5 Hz linear acceleration. Susceptibility--defined by incidence, frequency, and/or latency of emesis--was significantly higher in Bolivian than Colombian phenotypes, in the presence of visual cues, in males, but not at different periods of the day or with two successive test exposures. Since the emetic responses were quite similar to man in the eliciting motion stimuli, it was concluded that the squirrel monkey represents a very suitable primate model for studies of motion and space sickness.

Localization of cellular changes within multimodal sensory regions in aged monkey brain: possible implications for age-related cognitive loss.

Young (4 to 7 years) and aged (18 to 28 years) rhesus monkeys were sacrificed and various neuromorphometric analyses performed to determine age differences in gross topography, cell population and patterns of cellular degeneration. Two brain regions implicated for their role in age-related cognitive disturbances, the hippocampus and the gyri bordering the principal sulcus in the frontal cortex were selected for these comparisons. Reliable morphometric differences between age groups were observed in both neural areas. One significant difference observed in the hippocampus was a reduced mean depth of the pyramidal layer of the CA-1 zone in the aged monkeys. Also, the mean number of neurons per transverse section in the CA-1 zone of the pyramidal layer was significantly less in the aged monkeys, and in certain instances cell gaps were observed in this region. In the lateral principal gyrus of the frontal cortex, the number of neurons in full-depth "cores" was lower in the old monkeys, glial count was higher and the ratio of neurons to neuroglia, therefore, lower in the older monkeys. Further, the mean area of the principal gyri, measured planimetrically from the apex of the medial gyrus to that of the lateral gyrus was significantly smaller in the aged monkeys. These findings indicate that significant age-dependent cellular differences occur in brain areas thought to be functionally involved in the particular cognitive behaviors most severely impaired in aged monkeys. These differences in brain morphology may, therefore, help provide some leads into the types of neurological changes contributing to the severe cognitive disorders suffered by the elderly.