Opiate antagonists suppress ACTH1–24-induced excessive grooming in the rat

Intraventricular injection of ACTH_1–24 in rats induces excessive grooming behavior, and subsequent peripheral administration of specific opiate antagonists suppresses this peptide-induced grooming response. Intraventricular injection of morphine mimics both in intact and hypophysectomized rats' — to a certain extent — peptide-induced grooming. The results suggest similarities in the interaction of morphine and ACTH_1–24 with central nervous structures.     

Intrathecal FMRFamide (Phe-Met-Arg-Phe-NH2) induces excessive grooming behavior in mice

The molluscan neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) was administered intrathecally (i.t.) to mice and their behavior was monitored for 30 min. FMRFamide induced a dramatic and dose-related (5-12 micrograms) increase in grooming-related activities compared to saline-treated controls. The grooming behavior produced by 8 micrograms FMRFamide was not blocked by simultaneous i.t. administration of 10 micrograms of the following antagonists: atropine, phentolamine, methysergide, naloxone or spantide; peripheral administration of naloxone (3.5 mg/kg, s.c.) also failed to antagonize FMRFamide grooming. These data constitute the first report that FMRFamide produces behavioral changes in mammals.     

The effects of ACTH- and vasopressin- analogues on CO2-induced retrograde amnesia in rats

Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO₂ until respiratory arrest occurred. The ACTH-analogue ACTH_4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. The behaviourally inert ACTH-analogue ACTH_11–24 appeared to have no effect on the amnesia. The vasopressin-analogue desglycinamide lysine vasopressin (DG-LVP) antagonized the amnesia when administered 1 hr prior to the acquisition trial or 1 hr prior to the test trial. The relevance of these date to present theories on amnesia is discussed.     

Blockade of 5-hydroxytryptamine (serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep.

Recent data suggest that interleukin-1-induced enhancement of non-rapid eye movement sleep is mediated, in part, by the serotonergic system. To determine if sleep changes induced by interleukin-1 are mediated by a specific serotonergic receptor subtype, we evaluated interleukin-1 effects on sleep in rats pretreated with the 5-hydroxytryptamine (serotonin)-2 receptor antagonist ritanserin. Ritanserin (0.63 mg/kg, intraperitoneally) by itself did not alter sleep-wake behavior, although it did reduce cortical brain temperature. Interleukin-1 (5 ng, intracerebroventricularly) enhanced non-rapid eye movement sleep, suppressed rapid eye movement sleep, and induced a moderate febrile response. Pretreatment with ritanserin completely blocked the febrile response to interleukin-1 and abolished the interleukin-1-induced enhancement in non-rapid eye movement sleep that occurred during postinjection hours 3-4, without altering interleukin-1 effects on rapid eye movement sleep. The present data suggest that serotonin may partially mediate interleukin-1 effects on sleep by interacting with 5-hydroxytryptamine (serotonin)-2 receptors. These results also suggest that interactions between the serotonergic system and interleukin-1 may be important in regulating sleep-wake behavior.     

Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke

Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1-7) [Ang-(1-7)] and stimulation of the Ang-(1-7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1-7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1-7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1-7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1-7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1-7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1-7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2-Ang-(1-7)-Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1-7) protective action includes blunting of inducible nitric oxide synthase expression.     

ACTH(1-24)的应用研究进展

失血性休克是临床上最常见的休克类型。促肾上腺皮质激素(adrenocorticotrphin,ACTH)的N端24肽[ACTH(1-24)]通过迷走神经抗炎通路的激活能快速、高效地发挥抗休克作用,并能降低休克的炎性连锁反应及显著减轻休克后器官的损伤和功能障碍,这将为新型药物的开发和急性失血性休克的治疗开辟新的领域。     

Age-related changes in grooming behavior and motor activity in female rats.

The influence of hormonal status and the age of the rat on the expression of grooming behavior and motor activity were studied. Grooming, locomotion, and rearing were measured in young (4-months-old), adult (6-8-months-old), and old (18-months-old) female rats, during the estrous cycle. These behavioral performances were influenced by the hormonal changes that occur in young and adult female rats during the estrous cycle. In old rats there were no significant differences among the different days of the estrous cycle. A significant age-related decrease in grooming behavior and motor activity was also found. Locomotion and rearing were the parameters most affected by age. These findings could be related to: (a) the gonadal hormonal status, which appears to be able to modulate behavioral responses; and (b) the age-related changes, which may affect the normal display of these behaviors. The possible role of central peptidergic, cholinergic, and dopaminergic neural systems is discussed.     

Behavioral changes in aging female C57BL/6 mice

Using a range of tests we have studied alterations in behavior with advancing age in female C57BL/6 (of Jackson origin), the golden standard on which most genetically engineered mice are back-crossed. In parallel, growth and survival data were collected. In a protected environment the 90% and 75% cohort survival age was 20 and 25 months, respectively, and the 50% cohort survival was 32 months. In mice, body weight increases continuously until 15-20 months of age, while in advanced age whole body weight drops. The body mass loss in senescence is associated with emergence of other aged phenotype features such as kyphosis, balding and loss of fur-color.Our behavioral data show that aging modulates certain aspects of basic behavior in a continuous manner, like explorative and locomotor activities. Advanced age associates with an acceleration of behavioral impairments evident in most of the tests used, including motor skill acquisition and memory consolidation. However, certain domains of mouse behavior were well preserved also in advanced age such as thermal noxious threshold and working memory as assessed by an object recognition task. The decreased drive to explore is suggested to be a key factor underlying many aspects of reduced performance including cognitive capacity during aging. Behavioral aging affects genetically closely related individuals housed under strictly standardized conditions differentially (Collier, T.J., Coleman, P.D., 1991. Divergence of biological and chronological aging: evidence from rodent studies. Neurobiol. Aging, 12, 685-693; Ingram, D.K., 1988. Motor performance variability during aging in rodents. Assessment of reliability and validity of individual differences. Ann. N.Y. Acad. Sci., 515, 70-96). Consistent with this a subpopulation of the 28-month-old mice showed an explorative activity similar to young-adult mice and a significantly stronger preference for a novel object than aged mice with a less explorative behavior. Thus, subtle environmental factors and epigenetic modifications may be important modulators of aging.     

Reciprocal antagonism between ACTH1-24 and beta-endorphin in rats

ACTH1-24 and beta-endorphin simultaneously injected at 5-10 microgram dose into the lateral ventricle, reciprocally suppress most of their respective behavioural effects (stretching-yawning syndrome, sexual excitement and hyperalgesia for ACTH1-24 and catalepsy and analgesia for beta-endorphin). The results obtained support the hypothesis that ACTH1-24 and beta-endorphin might interact antagonistically at CNS level.     

Behavioral effects of angiotensin II and angiotensin II-(4-8)-pentapeptide in rats

One nM of angiotensin II (AII) or angiotensin II-(4-8)-pentapeptide [AII(4-8)] given intracerebroventricularly did not affect locomotor and exploratory behavior of rats in open field. AII significantly increased and AII(4-8) did not affect vertical activity of animals in electromagnetic motimeter. Neither of the peptides influenced horizontal activity in the motimeter. Both peptides intensified stereotypy produced by apomorphine and amphetamine. AII significantly improved, while AII(4-8) did not affect, consolidation of memory of the correct way to food in T-maze. Similarly, AII increased and AII(4-8) did not change the rate of acquisition of conditioned avoidance responses in a shuttle-box. Of the two examined peptides only AII significantly improved retrieval of memory of the passive avoidance behavior. The results show that AII(4-8) influences central dopaminergic system but, unlike its parent peptide AII, has no apparent effect on memory.     

Quantitative studies of monoclonal antibody 5-1-6-induced proteinuric state in rats.

Murine monoclonal antibody (MoAb) 5-1-6 was already reported to bind to epithelial cell foot processes and to cause proteinuria in rats. In vivo kinetics of the injected MoAb 5-1-6, relationship between the quantity of kidney-binding antibody and proteinuria, and changes in the amount of antigenic molecule recognized by this MoAb in the proteinuric state were studied. The amount of total kidney-binding antibody (TKAb) as determined 1 h after a 2 mg administration was 50.8 +/- 10.4 micrograms/2 kidneys, and TKAb declined to 1.9 +/- 0.4 at day 15. The minimum dose of MoAb required to induce proteinuria was 125 micrograms as the injected dose. This dose corresponded to 12.8 micrograms of TKAb at 1 h and 0.34 micrograms of TKAb at day 5. The amount of MoAb 5-1-6 binding to isolated normal glomeruli was also shown to exceed 147.7 micrograms/76,000 glomeruli, indicating proteinuria to be induced provided more than 8.7% (= 12.8/147.7) of the critical epitopes is specifically occupied by MoAb. The total amount of MoAb 5-1-6 bound to glomeruli in vivo and in vitro was assayed with [125I]-labelled anti-mouse IgG. The amount of [125I] anti-mouse IgG bound to glomeruli was 6.93 +/- 0.45 micrograms/10,000 glomeruli from rat 5 days after this MoAb injection and 26.58 +/- 0.66 micrograms/10,000 control glomeruli, indicating the decrease in the number of MoAb 5-1-6-recognized antigen molecules in glomeruli isolated from the rat in proteinuric state induced by this MoAb. Thus, the MoAb 5-1-6-recognized molecule itself may principally function to regulate the permeability of the glomerular capillary wall and the decrease of the molecule may lead to proteinuria.     

D-半乳糖衰老大鼠性腺轴系超微结构的变化

目的:观察D-半乳糖衰老大鼠性腺轴系超微结构的变化。方法:D-半乳糖连续腹腔注射制作亚急性衰老的大鼠模型,应用透射电镜观察模型大鼠下丘脑弓状核、垂体及睾丸超微结构的变化。结果:D-半乳糖衰老大鼠弓状核出现线粒体嵴断裂、粗面内质网脱颗粒、高尔基复合体扩张等变化;垂体促性腺激素细胞出现线粒体嵴断裂、粗面内质网扩张、高尔基复合体扩张等变化,并观察到脱粒细胞;睾丸支持细胞内溶酶体增多,内质网增生、扩张,线粒体嵴断裂,精原细胞可见胞质内出现许多空泡,并观察到了凋亡小体。结论:D-半乳糖衰老大鼠性腺轴系的超微结构发生了明显改变,揭示了D-半乳糖衰老过程中下丘脑垂体性腺轴的重要作用。     

大鼠心肌细胞超微结构的增龄变化

目的：探讨心肌细胞超微结构增龄变化的规律。方法：取健康雄性大鼠，电镜观测左心房和左心室细胞超微结构的形态和定量变化。结果：随年龄增长，心房肌节长度、线粒体数量各年龄段间无差异，心室肌节长度、线粒体数量各年龄段间存在显著差异；闰盘逐渐典型、复杂；心房中心钠素颗粒不断增多。结论：心房肌节长度、线粒体数量一生中基本不变；幼年到青年为心室肌节和线粒体迅速发育期；心室肌原纤维增长既有肌节数目增多，又有肌节长度增加。     

ADCC in aging rats with methylcholanthrene-induced sarcoma (MC-Sa)

Investigations on the relationship between the aging of the immune system and the tumor growth are the trigger of our studies. The purpose of the present paper was to determine a relation between cytotoxic activity of the spleen lymphocytes in ADCC assay and the MC-induced sarcoma growth in adult and aging rats. In ADCC assay the mouse leukemia L1210 labeled with Cr and sensitized with rabbit anti-L1210 serum was used as target cells. In aging rats with MC-Sa tumors the lymphocyte activity in ADCC was increased or remained unchanged in the comparison with normal animals. On the contrary, in adult rats with MC-Sa tumors ADCC activity was decreased. In comparative studies between the groups of adult and aging rats a reverse relationship between the tumor growth and the lymphocyte activity in ADCC was found. In aging rats the level of ADCC was higher than in adults, but the tumor growth was slower. We suggest that ADCC phenomenon may be involved in an antitumor response, especially effective in aging rats.     

Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin

UL24 of herpes simplex virus 1 is important for efficient viral replication, but its function is unknown. We generated a recombinant virus, vHA-UL24, encoding UL24 with an N-terminal hemagglutinin tag. By indirect immunofluorescence at 9 h post-infection (hpi), we detected HA-UL24 in nuclear foci and in cytoplasmic speckles. HA-UL24 partially co-localized with nucleolin, but not with ICP8 or coilin, markers for nucleoli, viral replication compartments, and Cajal bodies respectively. HA-UL24 staining was often juxtaposed to that of another nucleolar protein, fibrillarin. Analysis of HSV-1-induced nucleolar modifications revealed that by 18 hpi, nucleolin staining had dispersed, and fibrillarin staining went from clusters of small spots to a few separate but prominent spots. Fibrillarin redistribution appeared to be independent of UL24. In contrast, cells infected with a UL24-deficient virus retained foci of nucleolin staining. Our results demonstrate involvement of UL24 in dispersal of nucleolin during infection.     

Behavioral effects of basal forebrain cholinergic lesions in young adult and aging rats

The interactive effects of age and cholinergic damage were assessed behaviorally in young and middle-aged rats. Rats were lesioned at either 3 or 17 months of age by injection of 192 IgG-saporin immunotoxin into the medial septum and the nucleus basalis magnocellularis, and they were then tested on a range of behavioral tasks: a nonmatching-to-position task in a T-maze, an object-recognition task, an object-location task, and an open-field activity test. Depending on the task used, only an age or a lesion effect was observed, but there was no Age X Lesion interaction. Middle-aged and young rats responded to the cholinergic lesions in the same manner. These results show that in the middle-aged rats in which cholinergic transmission was affected, additional injury to the system was not always accompanied by major cognitive dysfunctions.     

Clinical and electroencephalographic changes in MMP+-induced parkinsonian syndrome in rats

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. Laboratory of Psychopharmacology and Group for Synthesis of Physiologically Active Compounds, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 2, pp. 147–150, February, 1989.     

Action of acth(1 -24) upon plasma corticosterone concentrations in racing pigeons (Columba Livia domestica)

To establish the optimal dose and sampling times for the ACTH stimulation test in racing pigeons, plasma corticosterone concentrations were measured in experimental animals at 0, 30, 60, 90, 120 and 150 min after intramuscular administration of different doses of ACTH(1-24). Baseline corticosterone concentrations varied between less than 0.2 and 1.24 mutg/dl. To evaluate adrenocortical function the clinician is advised to take a blood sample before and at 60 or 90 min after stimulation with 50 mug ACTH or at 30, 60, 90 or 120 min after stimulation with 125 mug ACTH. In healthy individuals a ten- to hundred-fold increase over baseline (t=0) corticosterone concentrations and absolute concentrations in the range of 2.2 to 15.0 mug/dl can be expected in the post stimulation sample.