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Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness. The present study was conducted in the head-down-tilt (HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30 degrees for two weeks on a 12/12 light/dark cycle. During this period, body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected i.v. with a solution containing 4 microcuries of nicotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain, blood, trachea, salivary gland, lung, heart, esophagus, spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determined and calculated as percent of total injected radioactivity. Final body weights of suspended animals were significantly (P < 0.05) lower than those of controls (309 +/- 21 vs 350 +/- 11 g). 3H-Nicotine was retained in greatest amounts by the kidneys, followed in order by salivary glands, spleen, and gastrointestinal tissues. Compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues: esophagus (25%), aorta (25%), fundus (25%), trachea (22%), adrenals (18%), spleen (17%), and pancreas (12%). The decreased retention of nicotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differences in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

The hypothalamo-pituitary-adrenal axis appears to play an important role in regulating the circadian fluctuations of brain-gut peptides, as well as the cell cycle of the gastrointestinal mucosa. Since dexamethasone treatment tended to restore circadian fluctuations lost to adren-x, the influence of adrenal glucocorticoids in the coordination of the rhythms of regulatory peptides and cell cycle kinetics appears to be substantial.

This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.

Effects of cholecystokinin octapeptide (CCK-8) on feeding behavior were examined in male and female rats. After an 18-hour fast, ad lib food intake for 30 minutes was measured for each rat. In male rats, food intake measured for 30 minutes was significantly decreased by intraperitoneal injection of 0.25 to 1 microgram/kg of CCK-8 in a dose-dependent manner. The satiety effect of CCK-8 was blocked by L-364,718 (20 nmol/kg), a specific cholecystokinin receptor antagonist. In female rats, food intake at proestrus and estrus was significantly less than that at diestrus. Food intake of female rats at diestrus and metestrus was significantly decreased by an intraperitoneal injection of CCK-8 prior to feeding, but it was not affected at proestrus and estrus. The effect of CCK-8 on food intake at diestrus and metestrus was dose dependent and was nearly abolished when 20 nmol/kg of L-364,718 was administered simultaneously. The results of this study suggest that stages of the estrous cycle affect feeding behavior of rats. Further, cholecystokinin's regulatory action on feeding behavior appears to be effective at diestrus and metestrus, but not at proestrus and estrus.

This study was conducted to investigate the role of humoral factors in pancreatic alterations induced by obstructive jaundice (OJ) in rats. OJ in male Sprague-Dawley rats induced significant increases in pancreatic weight, DNA content, and RNA content of acinar cells. These changes were accompanied by enlargement of eosinophilic granules and compressed nuclei. Protein, amylase, and trypsinogen contents of pancreas were also increased in OJ rats. In addition, plasma levels of bilirubin, cholecystokinin (CCK), and estradiol increased in OJ rats and were correlated positively with each other and with pancreatic weights. Administration of a specific CCK receptor, L-364,718, to OJ rats partly attenuated the changes of the pancreas, indicating that CCK is involved in these changes. These findings suggest that estradiol may be involved in regulating the pancreatic changes induced by OJ in rats.

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Altered protein diets and circadian rhythms of gastrin and cholecystokinin (CCK) were investigated in 126 male and 126 female Sprague-Dawley rats acclimated for two weeks to a 12:12 hr light-dark cycle. Rats were divided equally and fed low-protein (8%), high-protein (64%) or normal protein (27%) diets for four weeks. All animals were fasted for 24 hr prior to blood collections. Blood samples were collected at 4-hr intervals for 24 hr for determination of plasma gastrin and CCK using specific radioimmunoassays. A significant rhythm for gastrin was detected in males on normal and low-protein diets (P less than 0.03) and in females on low-protein diets (P less than .02). A significant rhythm for CCK was detected (P less than 0.05) in rats of both sexes fed normal and high-protein diets. Mean plasma levels of both peptides were lower in females than males. In a separate study, food intake and body weight were monitored in male rats receiving the three diets over 21 days. Animals on the low-protein diet exhibited reduced food intake and body weight compared to rats fed the normal or high-protein diets.

Fluctuations in serum gastrin and plasma cholecystokinin (CCK) over a 24-hr period were examined in fasted and freely fed adult BALB/c mice and Sprague Dawley rats. Eighty-four mice and 84 rats were caged in groups of (six) each and placed in separate isolation chambers with light from 0600 to 1800 hr (CST) daily (LD 12:12). After standardization for 30 days, one-half of the animals were fasted 24 hr prior to circadian sampling, and the remainder were allowed continuous access to food. Animals were removed and killed by rapid cervical dislocation every 4 hr beginning at 0800 hr for seven time points. Blood was collected and serum gastrin and plasma CCK were measured by specific radioimmunoassays. The data document a circadian bioperiodicity for serum gastrin and plasma CCK. The parameters of the rhythms, evaluated by cosinor rhythmometric methods, are characterized by an acrophase that occurs in the dark period for both fed and fasted rodents and a mesor that is higher in fed than fasted animals. Circadian sampling time and nutritional status appear to be important in studies involving serum levels of gastrin and plasma CCK in rodents.

Ventilatory regulation by brainstem sites rostral to the midpontile level was assessed in decerebrate cats by comparing the effects of punctate pneumotaxic center lesions with those of midpontile transection. After either procedure, PACO2 was significantly elevated. Moreover an equal suppression of hypercapnia-induced minute volumes and maintenance, at some PACO2 levels, of minute volume responses to hypoxia was observed. Tidal volume elevations accounted for the maintenance of hypoxia-induced minute volumes. Following pneumotaxic center lesions, hypercapnia-induced tidal volumes were higher than those exhibited subsequent to midpontile transection. After carotid sinus nerve section, PACO2 was elevated and hypoxia-induced alterations were abolished. Bilateral vagotomy resulted in apneusis. These data demonstrate that, in the brainstem area examined, only the pneumotaxic center influences the PACO2 level or set point for respiratory activity. A locus of tidal volume generation is ascribed to rostral brainstem sites outside this pneumotaxic center. Data obtained support the hypothesis of a differential brainstem integration of peripheral and central chemoreceptor afferent stimuli.

The effect of progesterone alone and in combination with estradiol was investigated in ovariectomized and gonadally intact female guinea pigs infected with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). The course of the infection, as determined by the percentage of cells with GPIC (chlamydia) inclusions in Giemsa-stained vaginal scrapings, was not affected in animals receiving 5.0 mg of progesterone daily. Progesterone had no influence on the enhancement of infection by estradiol. In comparison with sesame oil-treated controls, infection was prolonged by four to six days (P less than .05) in animals receiving a combination of 5.0 mg of progesterone plus 1.0 microgram of estradiol or 1.0 microgram of estradiol alone each day. In ovariectomized animals, estradiol delayed the appearance of IgA antibody in genital secretions, whereas progesterone alone had no effect. Guinea pigs treated with estradiol or progesterone plus estradiol manifested an acute endometritis not observed in animals treated with progesterone alone or in controls receiving sesame oil. Although cervical ectopy, analogous to that seen in women with high levels of progesterone, was identified by histopathology in animals treated with progesterone, no enhancement of the chlamydial infection was observed.

Some emotional disorders are associated with alterations of biological rhythm characteristics ('echronism'). Chronotherapy aims empirically to 1. optimize the kind and timing of conventional psychopharmacologic treatment and, need be, to use such old or new molecules in the rational endeavor to 2. correct (disease-determining) rhythm alteration directly. With respect to the first aim, a reduction by timing of undesired pharmacodynamic effects, as well as an amplification of empirically desired ones, can be dramatically illustrated by circadian rhythms in tolerance to many drugs affecting the central nervous system of rodents. A more rational approach is aimed at correcting ecchronism. The new antidepressant drug, nomifensine, achieves this task in rats with bilateral suprachiasmatic lesions, exhibiting in the telemetered core temperature an echronism of varying degrees. In this model system for the chronobiotic treatment of ecchronism, the properly timed administration of nomifensine speeds the adjustment of bilaterally (suprachiasmatically) lesioned rats to a shift in the synchronizing light-dark schedule. With methodologic provisions, notably for treatment timed by pertinent marker rhythms, nomifensine deserves clinical tests in psychochronotherapy.

The effects of bilateral electrolytic hippocampal lesions on voluntary ethanol selection were examined in five groups (n = 10 each) of male mice. Mice sustained lesions in the dorsal hippocampus (DH), central hippocampus (CH), ventral hippocampus (VH), were sham-operated (SH) or left unoperated. CH mice exhibited a preference for ethanol compared with all other groups (p less than 0.01). In a second experiment, ethanol preference threshold and 24-hour drinking patterns were examined in CH and SH mice. These data revealed a higher preference threshold in CH mice, but not difference in drinking activity periods compared with controls. The central hippocampal area may be important in ethanol ingestive behavior in mice.

Voluntary drinking responses to an alternating three-bottle, two-choice paradigm to tap water or to 5% ethanol were measured in adult male Fisher (Fshr; N = 14) and spontaneously hypertensive (SP; N = 16) rats for 6-9 days. All animals were singly caged and housed separately in isolation chambers. The animals received light from 0600 to 1800 (CST) daily (LD 12:12) or remained in constant darkness (DD) at room temperature (23 degrees C). Food was freely available. Water and ethanol bottles were changed daily, and volumes of the respective fluids consumed by each rat were measured. A dim red light (approximately 0.5 lux) was used in handling animals in the dark. SP rats demonstrated significant (P less than 0.05) circadian drinking patterns of water and ethanol consumption under LD and DD lighting conditions. Fshr rats, however, exhibited a circadian pattern (P less than 0.02) only with regard to water consumption under an LD 12:12 lighting schedule; they did not exhibit circadian patterns of drinking water (P less than 0.054) in DD or ethanol in LD (P less than 0.24) or in DD (P less than 0.67) conditions. Volumes of ethanol consumption were also greater (P less than 0.05) in SP rats than in Fshr rats. It is concluded that differences exist in circadian drinking behaviors for both water and ethanol intake in two strains of rats. Perhaps variation in circadian patterns is an evolutionary mechanism that programs behavior over an appropriate time span for differences in physiological needs of nocturnal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Lesions of the suprachiasmatic nuclei (SCN) have been reported to disrupt or abolish circadian rhythms of motor activity and body temperature as well as of several neuroendocrine functions. This study was undertaken to determine any effect the SCN may have on the prominent circadian rhythm characteristic of the mitotic index of the corneal epithelium. Singly caged adult mice of both sexes were fed ad libitum and standardized to 12 hours of light alternating with 12 hours of darkness. Animals were divided into experimental and control groups. Later they were killed in subgroups at the time intervals of 0800, 1200, 1000, 0000, 0400 hour. Mitotic counts were determined on both right and left corneas of all mice. The data were plotted separately for both groups and reflect colony variation. We conclude that major lesioning of the SCN or tis efferent projections disturbed but did not abolish the rhythm. In animals with unilateral lesions of the SCN, the mitotic index was consistently lower in the ipsilateral cornea. The mitotic index for animals with lesions which missed the SCN or its efferent projections did not differ from controls. The nuclei appear to function as pace-resetters and amplifiers of the rhythm studied.

Amygdalotomized, sham-operated and intact wild-derived house mice of both sexes were group-caged (8-10) or singly caged for 3 weeks. The weights of ovaries (p is less than 0.05) and uteri (p is less than 0.01) were less in intact and sham-operated grouped females compared to singly caged intact and amygdalotomized females. The weight of the reproductive organs in amygdalotomized grouped female mice was not different from singly caged controls. Body weights among amygdalotomized grouped females were heavier (p is less than 0.05) than singly caged controls. Seminal vesicle weights of intact and sham-operated grouped males were less (p is less than 0.05) than that of singly caged controls and grouped amygdalotomized males. Plasma LH values from the various groups coincided with the morphological data. These results support the hypothesis that increased population density impairs reproductive function in mammals. Perhaps the effects of decreased pituitary-gonadal function associated with overcrowding are mediated via amygdalar nuclei.

Female guinea pigs were treated daily with 1 mg of beta-estradiol-3-benzoate intramuscularly beginning 14 days before intravaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis and continuing during the course of the infection. Treatment with estradiol was found to markedly influence the course of genital infection with the chlamydial agent of guinea pig inclusion conjunctivitis, producing infections of greater intensity and longer duration than those in control animals. Moreover, pathogenesis was altered in that ascending infection was observed, resulting in endometritis, cystic salpingitis, and cystitis. Infection in the controls was limited to the cervix and vagina. Estradiol treatment increased the apparent number of infected cells in the cervix and vagina as detected by histopathology and immunofluorescent staining. Humoral and cell-mediated immune responses to the chlamydial agent of guinea pig inclusion conjunctivitis were comparable in estradiol-treated and untreated animals. These data indicate that hormonal manipulation may have profound effects on the course of chlamydial genital infections.

A circannual rhythm of Giardia lamblia positive stools was found by examination of records from three clinical laboratories in central Arkansas for the period 1980-1986. Cosinor analysis of monthly Giardia incidence based on stool specimen records from approximately 12,000 patients over the 7-year period revealed a circannual rhythm (P less than 0.001) on the basis of percent positive patients/month, with a computive acrophase occurring in late summer and minimum values in the winter. Patients involved in the study were primarily from the central Arkansas metropolitan areas, southern delta regions and northern mountainous regions of the state. Analysis of the data on the basis of total positive Giardia patients/month also revealed a circannual rhythm with the acrophase again occurring in late summer. The overall mean for percent positive stool specimens for the 7-year period was 5.3%, compared with the national average of 3.8% for G. lamblia positive stools. The data indicate that there may be a "Giardia season" in Arkansas since they could not be explained on the basis of day-care age distribution, or geographic origin. Awareness by epidemiologists, public health officials and other health care professionals of this circannual incidence of giardiasis is important for the prevention, diagnosis and treatment of this infectious disorder.

Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Counts of chlamydial inclusions in cells of vaginal smears collected during infection, showed prolongation and enhancement of infection in OC-treated animals as compared with controls. Appearance of IgG and IgA antibodies to GPIC in genital secretions, as determined by enzyme-linked immunosorbent assay (ELISA), was also delayed in OC-treated animals as compared with controls. OC-treated infected animals were killed on days 15 and 43, and gross pathological evidence for ascending infection culminating in salpingitis was found in all of five and four of five animals, respectively. On the other hand, among untreated infected controls on each sacrifice day, only one of five animals had any evidence for ascending infection. Chlamydiae were detected by light and electron microscopy in fallopian tube tissue collected on day 15 following OC-treatment but not in tissue from control animals.

Intraperitoneal administration of cyclophosphamide 100 mg/kg and 200 mg/kg significantly lowered plasma sodium and significantly increased plasma potassium but did not result in saline preference in a strain of wild-derived house mice given a choice between water and saline (0.15M) to drink. Deoxycorticosterone acetate treatment in dosages up to 1.5 mg for four days also failed to increase salt intake, The data suggest a possible absence of a sodium appetite mechanism in this species.

Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [3H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a "phase-resetter" and as a modulator of rhythm amplitude.

The effects of chronic administration of metyrapone, a specific adrenal 11beta-hydroxylase inhibitor, were examined on the reproductive organs of house mice. In one experiment, immature (30 days old) mice of both sexes received daily injections of either metyrapone (100 mg/kg) or saline ip for 30 days. In a second experiment, mature mice (90 days old) were treated in like manner either with metyrapone (100 mg/kg) or saline for 21 days. Twenty-four hours after the last injection, mice were killed, fixed in formalin, and organs were weighed and examined by light microscopy. There was significant impairment of ovarian and uterine development in the young female metyrapone-treated mice with the incidence of corpora lutea being reduced 82%. Seminal vesicle and body weights were significantly reduced in juvenile males. Among mature animals, a 14% decrease in adrenal gland weight from adult females was the only signigicant effect of prolonged treatment with metyrapone. These data support the hypothesis that increases in pituitary-adrenocortical function may impair development of reproductive organs in small rodents.

The effect of various doses of estradiol on genital tract infection by the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC) was investigated in ovariectomized guinea pigs. Prolongation of infection, as determined by chlamydial inclusion counts of cells in Giemsa-stained smears of vaginal scrapings, was observed in animals receiving daily doses of 1.0, 10.0, 100.0, or 1000 micrograms of estradiol. In contrast to controls, ascending infection resulting in endometritis was found in animals receiving doses of greater than or equal to 1.0 microgram of estradiol per day. Response to estradiol treatment was reflected in an increase in cervical-uterine wet weight and uterine wall thickness. No differences were observed in time of appearance of antibody titers to GPIC in serum, but a delay in appearance of IgA antibody to GPIC in genital secretions was found in estradiol-treated animals receiving doses of greater than or equal to 1.0 microgram per day.