Tilt Cage Research Articles

Environmental stress and vestibular inputs modulate cardiovascular responses to orthostasis in hypertensive rats.

The frequent accompaniment of hypertension by orthostatic circulatory disorders prompted us to investigate the effect of repeated and sustained head-up and head-down tilt positions on cardiovascular responses in spontaneously hypertensive rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused a transient elevation in blood pressure (7.3±1.7 mmHg) and heart rate (39.7±10.5 BPM), while repeated antiorthostasis led only to reversible tachycardia (85.6±11.7-54.3±16.8 BPM) in spontaneously hypertensive rats. In contrast to the Wistar rats, sustained tilt failed to affect the blood pressure or heart rate in spontaneously hypertensive rats because the environmental stress of being placed in horizontal tilt cages prior to the sustained tilt test induced marked changes in cardiovascular parameters. Non-specific stress responses were eliminated both by the anxiolytic diazepam and a sub-anesthetic dose of chloralose. Unlike diazepam, chloralose amplified the orthostatic pressor responses in the Wistar rats. In contrast to diazepam preventing the pressor response and associated tachycardia in spontaneously hypertensive rats, chloralose elicited this effect during both sustained orthostasis (36.0±7.3 mmHg, 63.7±21.8 BPM) and antiorthostasis (42.9±10.9 mmHg, 82.8±25.4 BPM), with a reduced baroreflex sensitivity. However, during sustained orthostasis, removal of the vestibular input led to a depressor response with bradycardia (12.5±3.2 mmHg, 59.3±17.3 BPM), whereas antiorthostasis only reduced blood pressure (20.5±7.1 mmHg) in the spontaneously hypertensive rats. We conclude that repeated tilts induce a transient pressor response and/or tachycardia in spontaneously hypertensive rats. Cardiovascular parameters are suppressed by diazepam, whereas chloralose evokes both blood pressure and heart rate responses during sustained tilts, which are primarily elicited by baroreflex suppression in hypertension. Vestibular inputs support cardiovascular tolerance to sustained postural changes in a rat model of human 'essential' hypertension.

The neuroprotective effects of voluntary exercise in a restraint stress model

Cell damage and cell generation can be altered in a stressed and exercised brain. However, it is not known whether voluntary exercise can prevent cell damage or cell death in stress situations, especially in the striatal region. To address this question, male Sprague-Dawley rats (3 months old) were separated into three groups (sedentary, restraint stress, and voluntary exercise+ restraint stress groups). The stress circumstances were restraint stress, light stress, and tilt cage. To assess cell damage, staining for the heat shock protein (HSP90) was undertaken and the numbers of cells showing positive HSP90 expression were counted. Neurogenesis was investigated by staining for nestin markers. The restraint stress effects were assessed by determining the number of HSP90 expressed cells produced in the dorsal striatum. A significant difference was found when the number of HSP90 positive cells in the restraint stress and the voluntary exercise+ restraint stress groups were compared to those in the sedentary control group. In both experimental conditions there was neurogenesis in the striatal area. However, the group that received voluntary exercise presented a significantly higher number of nestin-expressing cells over the restraint stress group. Voluntary exercise might have an adaptive effect on neurogenesis in terms of replenishing the cellular stressed neurons but it has no effect on ameliorating the level of stress marker. The evaluation of the effects of voluntary exercise on neurogenesis in the striatal region in the stressed model might contribute to a better understanding of beneficial interventions in movement disorders related to patients with depression.

Does Chronic Experimental Head-Down Tilt Alter Intramural Innervation Density of Limb Blood Vessels?

Earlier, substantial increases in the intramural sympathetic innervation density of rat hind-limb blood vessels were found after 2 weeks of experimental orthostasis with tubular 45 degrees head-up tilt cages. In the present study, we presumed that chronic head-down tilting induces opposite changes in the innervation density. Tilted rats were kept 45 degrees head-down in long tubular cages for either 2 or 4 weeks (HDT2, HDT4), and the control animals were maintained in horizontal tilt cages for the same period (HOR2, HOR4). Segments of the saphenous and brachial veins and arteries were used for quantitative electron microscopic examinations. Intramural innervation density was defined by nerve terminal density (NTD) and synaptic microvesicle count (SVC) within the vascular adventitia. Neither HDT2 nor HDT4 resulted in a decrease of NTD or SVC of the saphenous and brachial veins or arteries; instead, a tendency to increase was observed in some cases. Thus in contrast to the large increases we found earlier in hind-limb vascular innervation density after 2 weeks of head-up tilting, head-down tilting of the same duration-or even twice as long-did not decrease the adventitial innervation density in our model. We assume that the quasi-free locomotor exercise the tilted animals in the long tubular cages were allowed may counteract a possible suppressive effect of chronic head-down tilt on hind-limb vascular innervation density.

Behavioral and biochemical studies of the substrates of median raphe lesion induced hyperactivity

Many authors have demonstrated that electrolytic lesions of the median raphe nucleus lead to dramatic hyperactivity, but little is known as to the neural substrates of this effect. In the current series of experiments we investigated this question by examining locomotor activity and forebrain serotonin levels after the placement of wire knife cuts in various locations around the median raphe. Activity was measured in a five minute open field test and a one hour tilt cage test. Knife cuts designed to transect the major ascending serotonergic projections of the median raphe led to a pronounced depletion of forebrain serotonin, but had no effect on locomotor activity in either testing situation. Knife cuts located antero-ventral to the median raphe, designed to interrupt raphe connections with the ventral tegmental area and interpeduncular nucleus, increased activity in the tilt cage but not in the open field test. These cuts produced only small effects on forebrain serotonin levels. Knife cuts caudal to the median raphe failed to influence forebrain serotonin levels, but produced a significant increase in both open field and tilt cage activity. The effects of the posterior and the anteroventral cuts on tilt cage locomotion were additive, suggesting that different fiber systems were damaged by the two cuts. These results demonstrate that it is possible to double dissociate changes in forebrain serotonin levels and locomotor activity with lesions in the vicinity of the median raphe and further show that ascending projections are unlikely to be the only pathways involved in the effects of median raphe lesions on locomotor behavior.

Suppression of the rat’s locomotor activity at low intensities of electric footshock

Over 50% of all just noticeably different footshock intensities lie below ,3 mA for rats. Unfortunately, the suppression of the rat’s locomotor activity by low-intensity footshock precludes the use of these shock intensities in active escape or avoidance training. This activity-suppression effect was demonstrated in an alley and in a tilt cage. One explanation of this effect is that rats remain relatively immobile in order to avoid painful peaks in current density that occur when the animals’ paws make or break contact with “hot” grids. If this explanation is correct, the activity-suppression effect should be more pronounced with higher impedance shock sources. Some evidence is reported that is consistent with this explanation.

Is there sign-tracking in aversive conditioning?

The present experiment studied the approach-withdrawal behavior of rats relative to conditioned stimuli (CS) that were paired with shock (paired), paired with absence of shock (unpaired), or that bore no temporal relation with shock (random). In the paired condition, the rats equally divided their time between the side of a tilt cage on which the CS was presented and the other side. In the random condition, the rats displayed a preference for the CS side. In the unpaired condition, the rats displayed a larger preference for the CS side. The range of preferences observed was small compared with that typically observed in appetitive sign-tracking. These results are consistent with a small aversive sign-tracking effect coupled with an unconditioned preference for the CS.

Hippocampal mediation of raphe lesion- and PCPA-induced hyperactivity in the rat

These experiments provide a direct test of the hypothesis that median raphe lesion- or PCPA-induced hyperactivity in the rat is mediated specifically by the hippocampus. Previous studies had shown that a marked depletion of hippocampal serotonin accompanied median lesion-induced hyperactivity. In the present studies, aspiration of the anterodorsal hippocampus of adult male rats prior to median raphe lesions or PCPA administration abolished the ability of both of these treatments to produce locomotor hyperactivity in animals chronically housed in tilt cages. Control lesions of the overlying dorsal cortex and corpus callosum were ineffective in blocking the hyperactivity produced by these two treatments. The possibility that serotonin depletion-induced hyperactivity was dependent on the pituitary was excluded by the fact that PCPA effectively elevated the activity of hypophysectomized rats. These data indicate that serotonin depletion-induced hyperactivity in the rat is mediated by the hippocampus.

Automated analyses of circadian rhythm activity of small arthropods

An automated apparatus is described which measures circadian activity rhythms of small invertebrates in darkness or in the presence of monochromatic light. Back-and-forth activity in tilt cages is measured without physical contact by magnet-activated reed switches. Four such cages are grouped around a mercury pen lamp, whose spectra lines can be selectively filtered, and all are placed in a large enclosure with light-baffling for complete control of intensity and color, delivered to each animal. Activity, measured as reed-switch closures, is counted digitally and punched out periodically onto paper tape. An interactive computer program reads, stores, plots, and further analyzes the data.

Differential behavioral and neurochemical effects following lesions of the dorsal or median raphe nuclei in rats

Locomotor activity and regional forebrain levels of serotonin (5-HT) were measured following the placement of electrolytic lesions in either the dorsal or median raphe nucleus of adult male rats. In the first two experiments, control lesions were placed in the brachium conjunctivum, and in the third experiment, a sham lesion group served as control. Median lesions significantly increased locomotor actiivity as measured in tilt cages, by 250–300% on the second day post-lesion, and this elevation stabilized at approximately 100% above control levels on day 9 post-lesion. There were no statistically significant differences in the amount of locomotor activity in the dorsal, brachium or sham lesioned groups on any post-lesion day. When the amount of 5-HT depletion was measured 5 days post-lesion, it was found that the dorsal (D) and median (M) lesions produced similar reductions in cerebral cortex (D — 40%; M — 31%); hypothalamus (D — 54%; M — 58%) and striatum (D — 50%; M — 29%). However, the effects of the two lesions were markedly different in the hippocampus. The dorsal lesion produced a non-significant 10% reduction in hippocampal 5-HT level, while the median lesion caused an 82% reduction. On the basis of these data it is hypothesized that a reduction in hippocampal 5-HT may account for the increased activity in the median lesioned group.

Feeding time entrainment of activity and self-produced illumination change in a squirrel monkey

Daily feeding time was changed or left the same for four 20-day replications (A, B, B, C) for one female squirrel monkey while quantifying tilt cage activity and number of illumination changes/hour. Periodic regression analysis indicated that a statistically significant circadian cycle (23.5-24.6 h) was present for each replication. In addition, significant Phase by Replication interactions verified that feeding time served as an effective entraining stimulus for the two dependent variables under investigation.

A comparison of the locomotor effects of 5-hydroxytryptamine and 5-hydroxytryptophan administered via two systemic routes

This study compared the effects of systemically administered 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) on tilt cage locomotor activity in rats. 5-HT was a more potent inhibitor of activity than 5-HTP via both the s.c. and i.p. routes. The effect of 5-HT itself was greater when administered i.p., whereas the effects of 5-HTP were independent of the route of administration. These results indicate that behavioral changesfollowing 5-HTP injection may be attributable to the peripheral effects of 5-HT.

Measurement of analgesia using a spatial preference test in the rat

Using a rectangular tilt cage, the aversive threshold to grid shock was defined as that intensity avoided 75% of the time. Each shock intensity (30, 60, 90, 120, and 150 μA) was presented for 10 min during the 50-min daily session. Various narcotic (codeine sulfate, meperidine hydrochloride) and narcotic antagonist (pentazocine, cyclazocine) analgesics, as well as a sedative hypnotic (sodium pentobarbital), were assayed using this procedure. Both the narcotic and narcotic antagonist analgesics reliably elevated the aversive threshold in a dose dependent manner. These results could not be accounted for in terms of drug induced sedation. Sodium pentobarbital, in agreement with the clinical literature, demonstrated poor analgesic properties and was able to reliably elevate the aversive threshold only in doses that severely hampered the execution of the escape response. This technique appears to be specifically sensitive to the analgesic properties of drugs. As such, it should be useful as a screening procedure in the development of new analgesics and for the investigation of possible mechanisms underlying drug addiction.

A method for determining the aversive threshold in the rat using repeated measures: Tests with morphine sulfate

The procedure described here provides an objective automated technique for the psychophysical assessment of the aversive threshold and allows the animal Ss to serve as their own controls. Sensitivity to drug effects, as well as comparisons between drugs, using the same animals are possible also. Using a rectangular tilt cage, the aversive threshold to grid shock was defined as that intensity avoided 75% of the time. Each shock intensity (30, 60, 90, 120, and 150 microA) was presented for 5 min on one side of the cage and then switched to the other side for 5 min, thereby forcing the animal to sample each shock intensity. Aversive thresholds were determined daily for each rat. The analgesic effects of morphine sulfate were compared to saline. Animals were tested for 3 days at each morphine dose level (2, 4, 8, and 16 mg/kg). Each 3-day morphine series alternated with 3 days of testing under saline. Significant differences were detected between saline and morphine at 4, 8, and 16 mg/kg.

Social preference in the guinea pig as a function of social rearing conditions and age at separation from the mother

To determine the effects of social rearing conditions and age at separation from the mother upon later social preferences, 120 guinea pigs were divided at birth into two basic groups, communals and isolates. Within the communal conditions, five groups of Ss remained with other guinea pigs throughout the experiment, but the mother was removed when Ss were 0, 4, 8, 16, or 30 days of age. Within the isolate condition, Ss were separated from both the mother and other guinea pigs at 0, 4, 8, 16, or 30 days of age and remained isolated throughout the experiment until testing. At 135 days of age, social preference was tested in a tilt-cage apparatus for 6 consecutive days, 15 min daily. One end of the tilt cage contained another guinea pig, while the other end was empty. Results showed that preference for another guinea pig was reliably greater for the communally reared Ss than for those beginning isolation at any age. The age at separation from the mother had little effect upon social-preference scores for either rearing condition.

A tilt cage technique for measuring auditory evoked potentials during avoidance conditioning

A tilt cage procedure is described in which cat subjects were trained to make a rocking response. This response introduced a self-imposed restraint so that the cat's position can be maintained in a controlled stimulus field. The resulting reduction in motor activity allows electrophysiological events to be recorded during avoidance conditioning.

The stability and control of conditioned noise aversion in the tilt cage.

Twenty-six rats were used to study the development of stable conditioned responding to terminate white noise (100 or 105 db) in a tilt cage apparatus. Preliminary work, with one end of the cage consistently associated with silence, demonstrated stability at a high level of cumulative noise-off time per session. Time spent at the noise-off cage end was unaffected by lay-off and showed adaptation to reversal of the cage end functions. Variability in reversal acquisition, insensitivity to stimulus intensity changes and persistence in remaining at one end of the cage in the absence of noise-termination contingencies indicated the need for more precise behavioral control. A schedule programming several reversals of the no-noise end at variable intervals within each session was developed. Performance on the latter schedule was characterized by stability of high noise-off times and also proved more sensitive than the preliminary method to stimulus intensity changes (55, 70, 100 db) as measured by both cumulated noise-off time and cage crossing rates. The ease of training combined with sensitivity to stimulus change and the lack of highly specific motor response requirements make this technique promising for use with animals potentially debilitated by drugs or surgical after-effects.

The Effects of Neonatal Irradiation on Postnatal Activity and Elimination

It has been demonstrated that neonatal irradiation has diverse anatomical and neurological effects on the nervous system (1-3). These studies have uniformly indicated, first, that the nervous system of the developing organism is radiosensitive, and, second, that the amount of damage is directly related to dosage and inversely related to the age of the organism at the time of exposure. Studies on the behavioral effects of radiation have produced less definitive results than the neurological and anatomical studies (4-6). Of these studies, relatively few have investigated the behavioral effects of irradiation delivered to the organism at birth (5). Therefore, this study focuses on irradiation delivered to the neonate and the effects of this treatment on activity and elimination. Emotional behavior has been inferred from a variety of dependent variables (open field activity, elimination, home cage emergence, food consumption in open field, etc.), and no consensus appears to have been reached with regard to its exact meaning (7). Thus, in this report we shall not use the term emotionality. Only descriptive terms such as activity, elimination, and latency will be employed. Furchtgott and Echols (8) studied the effects of X-radiation on activity and elimination in rats and found that: (1) neonatal irradiation (300 R) tended to depress tilt cage activity, whereas fetal irradiation significantly increased such activity; (2) open field motility was, relative to controls, significantly greater for fetally irradiated animals and significantly less for neonatally irradiated animals; (3) neonatally irradiated animals seemed to defecate less frequently in the open field than controls. Thus, neonatally irradiated animals responded in an aberrant manner when compared to the fetally irradiated (in late gestation) subjects as well as the control subjects. These investigators concluded that X-irradiation results in hyperemotionality.

EFFECT OF METHYLPHENIDATE ON SPONTANEOUS ACTIVITY, FOOD INTAKE, AND COLD TOLERANCE OF PROPYLTHIOURACIL-TREATED RATS

Dietary administration of methylphenidate to rats increases locomotor activity (tilt cage method) roughly in proportion to the logarithm of the dose ingested. The results suggest that a dose of 62 mg methylphenidate/kg body wt. per day increases activity level by 50%. At higher dose levels, a tolerance appears to develop and is characterized by high initial levels of activity (days 1 to 3) followed by reduction of activity to a new stable level (days 4 to 6). Methylphenidate increases activity level and decreases food intake and body weight of both hypothyroid (propylthiouracil-treated) and control rats subjected to ambient temperatures of 10, 15, 20, and 28 °C. It fails to increase the tolerance of hypothyroid rats either to chronic (10 and 15 °C) or to acute (5 °C) cold exposure.

The effect of various periods of confinement on activity in tilt cages.

The effect of various periods of confinement on activity in tilt cages.