Reentrainment in Golden Hamsters: Effect of Melatonin, Age and Neonatal Clomipramine Treatment

Golden hamsters (young: 3 month-old; old: more than 12 month-old; or neonatally treated with clomipramine - a serotonin/noradrenaline re-uptake inhibitor antidepressant) were initially entrained to a 14:10 light:dark cycle, and their reentrainment rate after a 6 h phase advance in the photoperiod was determined. Animals took between 6 and 9 days to reentrain. Melatonin (1 mg/kg, i.p.) accelerated reentrainment to the LD cycle in all groups, except for the clomipramine-treated hamsters. These results support an important accelerating effect of the pineal hormone melatonin on resynchronization, no longer observed in clomipramine-treated hamsters.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ～ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ∼ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

The Use of Space in Caged Golden Hamsters*

Das Verhalten des Goldhamsters in seinem Heimkäfig wurde untersucht. Obwohl die Tiere auf engem Raum lebten, war ihr Verhalten räumlich und zeitlich geordnet. Die Hamster fraßen und putzten sich bevorzugt am Schlafplatz, meistens während der Ruhezeit des Tages und besonders häufig kurz vor dem Einschlafen. Einige hatten einen besonderen, regelmäßig benutzten Freßplatz; auch putzten sie sich manchmal an anderen, anscheinend zufällig gewählten Orten. Kot entleerten sie überwiegend am Freßplatz, aber auch im ganzen übrigen Käfig verstreut. Zum Harnen suchten sie dagegen stets dieselbe, vom Schlafplatz abgelegene Stelle auf.     

Stressors, Including Social Conflict, Decrease Plasma Prolactin in Male Golden Hamsters

Following exposure to a stressor, plasma prolactin (PRL) rises in most species. The purpose of the present study was to examine the effect of social conflict or of footshock stress on PRL responsiveness in male Syrian hamsters. Contrary to expectations, PRL was significantly lower in subordinate hamsters than in their dominant opponents or in controls following one, five, or nine exposures to social conflict. Similarly, PRL was reduced in hamsters subjected to a mild footshock stressor. By contrast, adrenocorticotropin, another stress-responsive hormone, was elevated following exposure to each of these stressors. We also demonstrate that PRL release is inhibited by dopamine as it is in other species by showing that there is a dose-dependent increase in PRL release following treatment with the dopamine receptor blocker, domperidone.     

Infectivity of Leishmania donovani Amastigotes and Promastigotes for Golden Hamsters*

SYNOPSIS. Intracardial injection of hamsters with from 5 to 114 million amastigotes or promastigotes of Leishmania donovani and screening of the 8th-day liver impression smears, provides a rapid and reproducible method for assaying infectivity. Amastigotes are at least 10X more infective than promastigotes, and log-phase promastigotes act as a single infective population for hamsters.     

Population Control in Confined Colonies of Golden Hamsters (Mesocricetus auratus Waterhouse)

The mechanisms by which confined colonies of Golden Hamsters regulate the density of their population were investigated. Six experimental populations were established with two ♂♂ and two ♀♀ each and allowed to grow freely for 3–8 months. At no time did any population exceed eight individuals. This appeared to be the result of a high rate of infant mortality due to failure of pregnant and parturient ♀♀ to isolate themselves from the others. Two other populations were then established allowing many more nesting areas and more room for dispersal, but animals continued to crowd together and infant survival did not improve. These results contrast sharply with the large ultimate populations and only slowly developing disturbances seen in rats and mice. This difference in population control appears to be the direct result of a species difference in the tolerance of adults for strange newborns. In two further short-term experiments, the effects of the number and sex of adults in the founding population were systematically examined. The critical density at which no pups survived past the first day was six or more animals; ♀♀ appeared to contribute more than ♂♂ to infant mortality.     

Piracy and Privateers in the Golden Age: Lessons for Today

Customary international law has governed high seas piracy for many centuries and is now codified in the United Nations Convention on the Law of the Sea (LOSC). In this article, we discuss the reasons why enforcement against piracy today is less effective than three hundred years ago. We contend that crime, including the crime of piracy, can be modeled as a rational choice that is responsive to expected rewards and punishments. Based on this view, we argue that three hundred years ago, the free rider problem resulting from enforcement on the high seas was less prevalent than it is today because seaborne trade was more concentrated in the vessels of a few countries, making enforcement more like internal than international policing. The persistence of piracy today also stems from a continuing low probability of capture coupled with lenient punishments. In addition to enforcement differences, we contrast the sources of piracy in the two eras—in the earlier period, the end of privateering led many privateers to engage in piracy, whereas today, the main source of pirates in the Western Indian Ocean is the existence of a “failed state,” and off West Africa and South East Asia pirates are common criminals.     

Diurnal Variations in Cyclic AMP and Melatonin Content of Golden Hamster Retina

Abstract: The diurnal variations and photic regulation of cyclic AMP and melatonin content in golden hamster retina were studied. Both parameters showed significant diurnal variations with maximal values at night. Light exposure during the night inhibited retinal cyclic AMP and melatonin levels, whereas exposure to darkness during the day significantly increased cyclic AMP and melatonin content. Incubation with melatonin of retinas excised at different intervals indicated that the methoxyindole inhibited cyclic AMP accumulation in a time-dependent manner. The inhibitory effect of melatonin at 2400 h and at noon showed a threshold concentration of 1 and 10 pM, respectively. At 0400 h melatonin did not affect cyclic AMP accumulation. The results indicate a diurnal variability of retinal cyclic AMP and melatonin content in hamsters, mainly influenced by a photic stimulus. Cyclic AMP could be a putative second messenger for melatonin action in golden hamster retina.     

Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden Age

Ibn al-Nafis (1213-1288) was an Arab physician who made several important contributions to the early knowledge of the pulmonary circulation. He was the first person to challenge the long-held contention of the Galen School that blood could pass through the cardiac interventricular septum, and in keeping with this he believed that all the blood that reached the left ventricle passed through the lung. He also stated that there must be small communications or pores (manafidh in Arabic) between the pulmonary artery and vein, a prediction that preceded by 400 years the discovery of the pulmonary capillaries by Marcello Malpighi. Ibn al-Nafis and another eminent physiologist of the period, Avicenna (ca. 980-1037), belong to the long period between the enormously influential school of Galen in the 2nd century, and the European scientific Renaissance in the 16th century. This is an epoch often given little attention by physiologists but is known to some historians as the Islamic Golden Age. Its importance is briefly discussed here.     

不同种株利什曼原虫对Balb/c小鼠和金黄地鼠的致病性研究

为了比较不同种株利什曼原虫对实验动物的致病性,分别将5×107的杜氏利什曼原虫SC6株、热带利什曼原虫K27株、婴儿利什曼原虫LEM235株和婴儿利什曼原虫KXG-Liu株前鞭毛体与无鞭毛体感染Balb/c小鼠和金黄地鼠,观察各感染动物皮肤损害状况,3月后,有限稀释培养法分别检测肝和脾脏内的虫荷数.发现不同种株利什曼原虫引起的疾病存在极大的异质性,杜氏利什曼原虫四川SC6株致Balb/c小鼠轻微皮肤损害,肝和脾脏内重度虫荷数,金黄地鼠肝和脾脏内重度虫荷数;热带利什曼原虫K27株致Balb/c小鼠严重的皮肤损害,但肝和脾脏的虫荷数较低,金黄地鼠肝和脾脏中未查见原虫;婴儿利什曼原虫LEM235株致Balb/c小鼠严重的皮肤损害,肝和脾脏内重度虫荷数,金黄地鼠肝和脾脏内重度虫荷数;婴儿利什曼原虫KXG-Liu株可致Balb/c小鼠严重的皮肤损害,肝和脾脏中度虫荷数,金黄地鼠肝和脾脏内少量虫荷数.另外,还发现原虫的生活史状态和进入机体的途径及实验动物的类型对不同种株利什曼原虫感染致病产生影响.     

Influence of Genetic Factors on the Induction of Mammary and Intestinal Adenocarcinomas in Inbred Syrian Golden Hamsters

INBRED lines of Syrian golden hamsters, Mesocricetus auratus auratus, respond to subcutaneous injection of polycyclic hydrocarbons^1,2 and to oncogenic viruses³ with varying rapidity and tumour incidence, which depend on genetic factors. We have investigated the inherited susceptibility or resistance of Syrian hamsters to the development of intestinal and/or mammary adenocarcinoma after the administration, by stomach tube, of 250 mg of 20-methylcholanthrene (MC) in corn oil three times a week (5 mg in 0.5 ml.) for 17 weeks. Thirty males and thirty females aged 90 days of nine inbred strains were used and, after the course of MC gavage, they were left until they looked ill and were then killed. Autopsies were done between 4 and 39 weeks after the last MC feeding or at age 34–69 weeks in seven BIO lines (Telaco, Bar Harbor, Maine) (Table 1). At least eleven males or eighteen females survived for at least 4 weeks after the last feeding. The incidence of their tumours is shown in Table 2.     

Social Interaction is Necessary for Discrimination between and Memory for Odours of Close Relatives in Golden Hamsters

The role of social experience in recognition of individuals and their odours is not well understood. In a previous study, hamsters discriminated between the odours of their familiar litter mates, but they did not discriminate between the odours of two males or two females from a different litter that were unfamiliar to them. In this paper the role of social experience in discrimination between odours of male litter mates is examined using habituation techniques. Males, tested 1.5–2 mo after separation from their litter mates, discriminated between the flank gland odours of their foster brothers, but they did not discriminate between flank odours from their unfamiliar brothers that had been reared by another mother (Expt. 1). In Expt. 2, adult males did not discriminate between the flank gland odours of two males from a different litter after a week of exposure across a barrier to their sights, sounds, and odours, but subjects did discriminate between the odours of these same males after five brief encounters with them. A month after the encounters, however, subjects no longer discriminated between these odours. In contrast, adult males discriminated between the flank odours of their brothers 9 mo after separation from them (Expt. 3). These results suggest that hamsters must have direct interactions with closely related individuals to discriminate between their odours because the odours of close kin are so similar. Experience with nest mates results in long-lasting memories for their odours.     

Twice Daily Melatonin Peaks in Siberian but not Syrian Hamsters under 24 h Light:Dark:Light:Dark Cycles

The daily pattern of blood-borne melatonin varies seasonally under the control of a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin secretion and locomotor activity in Siberian and Syrian hamsters entrained to bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal arrangements of component circadian oscillators. Under LDLD, both species robustly bifurcated wheel-running activity in distinct day scotophase (DS) and night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin increases during each scotophase in LDLD, and in the single daily scotophase of LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16 h scotophases. Syrian hamsters, in contrast, showed no significant increases in plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this species, detectable levels were observed only when the DS of LDLD was acutely extended to yield 16 h of darkness. Established species differences in the phase lag of nocturnal melatonin secretion relative to activity onset may underlie the above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian hamsters show increased melatonin secretion within ～2 h after activity onset, whereas in Syrian hamsters, detectable melatonin secretion phase lags activity onset and the L/D transition by at least 4?h. The present results provide new evidence indicating multi-oscillator regulation of the waveform of melatonin secretion, specifically, the circadian control of the onset, offset and duration of nocturnal secretion.     

Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats

Objective

To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage.

Methods

A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3.

Results

Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro.

Interpretation

These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults.     

Hormonal Modulation of Cyclic Melatonin Production in the Pineal Gland of Rats and Syrian Hamsters: Effects of Thyroidectomy or Thyroxine Implant

Night-time pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the activities of the two enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase involved in the cyclic production of melatonin were determined in male albino rats and Syrian hamsters that were implanted with thyroxine or thyroidectomized two weeks earlier. Both treatments depressed nocturnal pineal melatonin content in rats and hamsters. The cause of this depression is not known, although minor alterations in the substrates and the enzymes involved in melatonin production were observed. The data suggest that alterations in thyroid hormone levels may increase the release of nocturnal melatonin from the pineal, thereby allowing less to accumulate in the gland.     

Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

Background

Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.

Methods

Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting.

Principal Findings

CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8^th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.

Conclusions/Significance

The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis process of C. sinensis induced CCA in hamsters.     

Effect of Poly I:C on Experimental Respiratory Infection in Hamsters

The interferon inducer double-stranded polyinosinic acid and polycytidylic acid (poly I:C) was studied in hamsters experimentally infected with parainfluenza 3 virus. Upper intranasal, deep intranasal, or intraperitoneal treatment of hamsters with poly I:C (100 mug/100- to 120-g animal) 24 hr before an upper respiratory infection significantly reduced the virus yields taken 28 hr after infection. Deep intranasal and intraperitoneal treatment with poly I:C greatly decreased the virus titers in the lungs, as measured 48 hr after a deep lung infection with parainfluenza 3 virus; however, the upper respiratory poly I:C treatment was ineffective.