Chiaki Hara

Plasma corticosterone response of rats with sociopsychological stress in the communication box

The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychologically stressed experimental group. In acute stress experiments, nonfoot shocked rats were exposed to emotional responses from foot shocked rats for 6 h in the light (0900-1500) or in the dark phase (2100-0300). In the light phase, the induced increase in plasma corticosterone levels of nonfoot shocked and foot shocked rats returned to corresponding control levels 6 h following the initiation of stress session, whereas those in the dark phase were significantly higher. Although there were some differences in corticosterone responses between both phases, the acute effect of sociopsychological stress was unclear. Chronic stress experiment with daily exposure for 1 h to sociopsychological stress caused the plasma corticosterone levels of nonfoot shocked rats to increase significantly not only in the postexposure level (just after stress exposure) but also in the preexposure level (before stress exposure) when naive rats were used daily as foot shocked animals. These results suggest that the repeated exposure of sociopsychological stress can induce physiological changes, and stressful situation can be established with only emotional responses from foot shocked rats.

Feeding conditions and estrous cycle of female rats under the activity-stress procedure from aspects of anorexia nervosa

The present study investigated the application of female rats with activity stress as an animal model for anorexia nervosa. Young female rats were singly housed in activity-wheel cages with food-restricted schedule (2, 3, or 4 h of food availability per day) for 3 weeks. Estrous cycle, body weight, food intake, and wheel revolution were recorded daily. Gastric pathology was also observed using the endoscopic technique. Rats that were subjected to either a 3- or 4-h feeding schedule exhibited the cessation of estrous cycle, loss of body weight, and suppression of food intake. These animals also showed a remarkable increase in running activity. However, they had no gastric lesions throughout the experimental period. On the contrary, the 2-h feeding schedule elicited severe gastric lesions and high mortality. The results suggest that behavioral and physiological changes of the young female rats with 3 or 4 h feeding share some symptoms of anorexia nervosa, although their anorexia is not self starvation.

Influence of activity-stress on thymus, spleen and adrenal weights of rats: Possibility for an immunodeficiency model

Abstract Rats were housed in standard activity cages under normal LD cycle (lights on 7:00–19:00) and fed 1 hr each day for 2 weeks. Control rats which were fed 1 hr each day in laboratory cages or fed freely in activity cages did not die and were ulcer-free. Incidence of rats with ulcer was higher in the group fed 1 hr in the nighttime than in the daytime group fed 1 hr in the morning, whereas the mortality was similar for both groups. The daytime group died sooner than the nighttime group. Thymus and spleen weights of rats exposed to activity-stress decreased considerably, while adrenal weights increased. The victims always revealed pulmonary infection, and the microscopic pathology of the thymus and spleen disclosed the lack of immunologically competent cells. Accordingly, these results suggest that rats exposed to activity-stress reveal, not only ulceration, but also immunosuppression. Stress factors and the possibility of utilizing the activity-stress rat for an immunodeficiency model are discussed.

Circadian rhythm of apomorphine-induced stereotypy in rats

The existence of circadian variations of apomorphine-induced stereotypy was determined. Male Wistar rats, standardized to a light-dark cycle (lights on from 7:00--19:00) for three weeks, were injected with apomorphine hydrochloride (1 mg/kg or 3 mg/kg) at one of six times (9:00, 13:00, 17:00, 21:00, 1:00 and 5:00). A significant time-of-day effect was found for apomorphine-induced stereotypy, with highest stereotypic score following injection at 13:00 or 17:00. The circadian rhythm of apomorphine-induced stereotypy was significantly fitted to a single cosine curve with a 24-hr cycle using the least squares method.

The activity-stress ulcer and antibody production in rats

Abstract Rats were divided into 4 groups: a control group fed freely for 7 days and three stressed groups fed 1 hr each day for 3, 5 and 7 days. All animals were housed in activity-wheel cages under a reversed LD cycle. They were immunized twice with sheep erythrocytes before beginning the stress schedule. All animals had blood samples collected from the retroorbital plexus and were sacrificed at Day 7, following the second antigen treatment for survivors and just prior to death for non-survivors. The stomach, lungs, thymus, spleen and adrenals were removed and examined histologically. The capacity of antibody production was assessed by the hemagglutination test. The incidence of rats with ulcer reached 60% in the 3-day stress group, although antibody production was unaffected and no rats died in this group. In the 5-day and 7-day stress groups, the incidence of rats with ulcer reached 90%, antibody production was significantly inhibited, and the degree of mortality increased to more than 50%. The severity of ulcer was in proportion to the length of stress periods. These data suggest that activity-stress rats have two pathological phases: stomach ulcer and immunodeficiency. The present study emphasizes that immunological response can serve as an indicator of the biological response for stress.

Influence of maturation on ulcer-development and immunodeficiency induced by activity-stress in rats

Young adult rats housed in the activity-wheel cages and fed only 1 hr daily, have ulcers in the glandular stomach and reveal immunodeficiency. The present study was attempted to investigate how to separate the ulceration and immunodeficiency in order to utilize the activity-stress (A-S) model as an animal model of the human stress ulcer. Six and 10 weeks old rats were used as subjects in this study. They were stressed for 3, 5, or 7 days. In the younger rats, the longer stress exposure caused to deteriorate more both the ulcer and immunodeficiency. The ulceration was found in all of the three stress periods, while the immunodeficiency was recognized in the 5- and 7-day stressed rats. In the elder rats, the ulceration was found in the 5- and 7-day stressed rats, whereas the immunodeficiency was seen only in the 7-day stressed rats. In the free-feeding control rats, relative weights of the thymus and spleen in the elder rats were smaller than those of the younger rats. In the adrenal weight, there was no difference between two age rats. The thymus and spleen of rats exposed to the stress revealed atrophy in both ages. These results suggest that immature rats are more susceptible for the stress than young mature rats, and application of mature rats to the A-S experiment appears to be available in the case of utilizing A-S rats as the stress ulcer model.

Characteristic of Learning Deficit Induced by Ibotenic Acid Lesion of the Frontal Cortex Related with the Nucleus Basalis of Meynert in Rats

The final goal of this study is to develop an animal model of Alzheimer’s disease (AD) for preclinical evaluation of therapeutic drugs. AD has classically been defined as a progressive dementia accompanied by characteristic neuropathological changes such as senile plaques and neurofibrillary tangles, both of which are hallmarks of AD. However, no animals having these neuropathological characteristics exist. On the other hand, the memory dysfunction of AD has been associated with a cortical cholinergic deficiency (DeFeudis, 1988). Therefore, memory dysfunction based on nerve cell loss of the cortex in animals may be adequate as an animal model of AD.

Evaluation of depression in rats exposed to chronic (unpredictable) electric shock

The present study was undertaken to evaluate the applicability of a proposed behavioral stress paradigm as an animal model for depression. Rats were trained to press a lever under a fixed ratio (FR) 5 schedule in a Skinner box for 10 days and were subsequently exposed to a daily regimen of 20 cycles of FR 5 and 10 cycles of variable ratio (VR) 10 for about a week. This exposure resulted in a reduction of the number of lever presses and successful escapes compared to the level achieved after training. In addition, weight gain was significantly suppressed compared with other treatments. Acute and chronic administration of psychotropic drugs (imipramine and chlordiazepoxide) showed that treatment with imipramine increased both the number of lever presses and successful escapes while chlordiazepoxide increased only the number of lever presses. The results suggest that this simplified animal model utilizing chronic unpredictable electric shock may be useful in the study of human depression.