Correlations between histamine and opioid peptides on the modulation of inflammatory processes in rats exposed to stress

The role of mast cell histamine in body reactivity of rats under experimental stressful conditions was studied. Animals submitted to chronic anaphylactoid reactions (by injecting compound 48/80 at the dose of 1 mg/kg, i.p., twice daily, for five days), when exposed to cold-restraint stress, exhibited a fully evident inflammatory response in the carrageenin-oedema test, whereas saline-treated rats, under the same experimental conditions, showed reduced paw oedema. Interestingly, a single injection of compound 48/80 increased the pituitary content of Beta-endorphin(ir), but chronic administration failed to produce this effect suggesting that some adaptation of the organism to repeated anaphylactoid reactions may occur.These results support the hypothesis of correlations between pituitary Beta-endorphin and mast cell histamine in the reactivity of the organism to stressful stimuli.     

Modification of a weak learning experience by memory retrieval in the day-old chick

Activation of memory retrieval after weak learning (WL), during either the short- or intermediate-term stages of memory in day-old chickens, resulted in the strengthening of the memory to levels normally associated with strong learning. Administration of the calcium channel antagonist lanthanum chloride, the glutamate receptor agonist monosodium glutamate, or the N-methyl-D-aspartate glutamatergic receptor antagonist AP5 prevented strengthening of a WL memory by reminder-activated memory retrieval. The results of this study are discussed in light of our recent findings suggesting two phases of memory retrieval in the day-old chick. The results are consistent with the proposition that a memory undergoing the processes of formation may be modified to include information gleaned at the time of memory retrieval and that a second phase of memory retrieval may be responsible for such modification.     

Expression of opioid peptides in tumors

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.     

Possible role of the opioid peptides in sleep

The opioid peptide endorphins, enkephalins, and dynorphins — found in brain, pituitary, and gut — are neurohormones involved in the regulation of a number of seemingly diverse biologic activities, including respiration, mood, pain perception, blood pressure, body temperature, and certain visceral responses. When viewed in integrated fashion, however, the spectrum of activities induced by the administration of both the exogenous opiates (e.g. morphine) and the endogenous opioids resembles a natural physiologic state: the sleep state.We propose that the opioid peptides in conjunction with the peptide neurohormone vasopressin are involved in the induction and maintenance of the sleep state. We also propose that the function of sleep is to protect an animal during periods when it is at a selective disadvantage, and we provide evidence to support and integrate both concepts.     

雌激素对阿尔茨海默病模型大鼠学习记忆的影响

目的:探讨雌激素对阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠学习记忆能力的影响。方法:选取雌性SD大鼠24只,随机分为假手术组、卵巢切除组(ovariectomy,OVX)、OVX+苯甲酸雌二醇组(estradiolbenzoate,EB),每组8只。于海马注射Aβ1-42建立AD大鼠模型,通过Morris水迷宫观察大鼠的学习记忆能力,同时用ELISA检测脑组织超氧化物歧化酶(super oxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、乙酰胆碱酯酶(acetylcholine esterase,ACh E)的活性,用免疫组化分析神经元型一氧化氮合酶(n NOS)并测定其OD值。结果:与OVX组比较,OVX+EB组逃避潜伏期明显缩短(P0.05),原平台象限活动时间明显增加(P0.05),穿越原平台次数明显增多(P0.05)。雌激素作用还提高大鼠脑组织SOD、ACh E和n NOS活性,降低MDA活性(P0.05)。结论:研究表明雌激素可改善AD模型大鼠的学习记忆能力,其机制可能通过提高脑组织SOD、ACh E和n NOS活性,降低MDA活性有关。     

Influence of isolation stress and inhibited protein biosynthesis on learning and memory in goldfish

Goldfish, Carassius auratus auratus L. (Pisces, Cyprinidae), were trained by different kinds of training procedures under the influence of cycloheximide or puromycin, two inhibitors of the protein biosynthesis. After active avoidance training in a shuttle box an apparent amnesia was found only when the fish were exposed to a one day lasting isolation stress prior to training. If the animals were accustomed to isolation over a period of 20 days the inhibitors did not affect memory formation. After learning by positive reinforcement (food rewarded color discrimination) in groups under stress-free conditions, neither learning nor memory formation were impaired in spite of the presence of cycloheximide. It is suggested that the amnestic effect of the inhibitors is caused by isolation treatment. Lack of the additional stress, however, leads to memory formation.     

The effects of peripheral endocrine hormone deficiencies on the processes of behavior, learning, and memory

The effects of thyroid and adrenal cortex hormone and sex hormone deficiencies on the ability to learn, store memory traces, and behave were compared in male rats. These studies showed that removal of peripheral endocrine glands led to disruption of the learning process and the ability to reproduce learned information and also produced alterations in behavior. Analysis of the results showed that corticosteroid hormones are directly involved in the processes of learning and behavior. Sex and thyroid hormones appear to have modulatory effects on higher nervous activity. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 49, No. 1, pp. 39–47, January–February, 1999.     

雌激素对阿尔茨海默病去势雌性SD大鼠学习记忆能力的影响

目的观察雌激素对阿尔茨海默病(AD)大鼠学习记忆能力的影响。方法首先采用Aβ1～40,1μL(10μg/μL)立体定位SD大鼠单侧海马内注射建立AD动物模型,二周后双侧卵巢切除术(OVX)制备去卵巢大鼠模型后给予雌激素替代治疗(ERT),最后通过Morris水迷宫观察动物模型的学习、记忆能力变化情况。结果 ERT组AD动物模型的水迷宫逃避潜伏期和目标象限游泳时间比OVX组明显缩短(P0.05)。结论雌激素具有改善AD大鼠模型认知功能的作用。     

Heterochronous involvement of neurotrophic factors in the neurochemical organization of learning and memory processes in adult organisms

Studies were performed on the involvement of neurotrophic factors in the neurochemical mechanisms of the integrative functions of the brain. The effects of various intrahippocampal doses of antibodies to neurotrophic factors – protein S100 and lectin CSL – were studied on the formation, retention, and reproduction of a habituated acoustic startle response and conditioned fear in adult rats. S100b contents in the hippocampus, hypothalamus, frontal cortex, and cerebellar hemispheres and vermis, and in the basal nuclei were measured in rat brains 0.5, 1, 2, 4, 6, 8, 24, and 48 h after long-term habituation to the startle response. Antibodies to neurotrophic factors had selective and dose-dependent effects on the different memory and learning processes underlying these types of behavior. Changes in S100b in brain structures were seen, which were specific in terms of quantitative levels and dynamics, after acquisition of the behavioral habit. The results obtained here, along with previously reported data on the effects of antibodies to S100b and CSL given into the cerebellum, are discussed as experimental support for the hypothesis of the heterochronous neurochemical organization of integrative brain activity.     

Effects of opioid peptides and naloxone on nervous tissue in culture

It was shown that opioid peptides stimulate nervous tissue growth in culture in the rat, which manifests itself in augmented outgrowth of neurites from explants and in an increase in the number of glial and fibroblast-like cells in the growth zone. The effects of opioid peptides ([Leu]- and [Met]-enkephalins, beta- and gamma-endorphins and some synthetic analogues of [Leu]-enkephalin) on the growth of organotypic cultures of rat sympathetic and dorsal root ganglia and spinal cord were investigated. Neurite outgrowth, cell composition, and size of the growth zone as well as the dynamics of its formation were estimated. Changes in the survival of neurons in dorsal root ganglion cultures were determined. The experiments were performed with living cultures as well as with fixed preparations. In experiments with sympathetic ganglia, it was demonstrated that a significant growth-promoting effect is exerted by peptides taken at concentrations of 10(-8) M to 10(-14) M. Naloxone does not eliminate the effects of peptides, but stimulates the growth at 10(-5) M to 10(-7) M. Studies with spinal cord revealed that naloxone (10(-6) M) enhances the response to [Leu]-enkephalin (10(-9) M). The survival of dorsal root ganglion neurons under the influence of a [leu]-enkephalin analog (10(-9) M) exceeds control values by approximately two to four times. Thus, opioid peptides were shown to exert a strong growth-promoting effect on nervous tissue in culture. This effect is dual: in neurons the peptides stimulate the outgrowth of neurites and their survival, while in glial cells they change the rate of their migration and, probably, their proliferation. It is suggested that opioid peptides, besides their already established functions, may play a role in the development and regeneration of nervous tissue.     

Influence of diet and occlusal support on learning memory in rats behavioral and biochemical studies

In order to verify the relationship between tooth loss and the learning memory in rat, male Wistar rats (25 weeks old) were divided into three separate groups: a control group (fed with a solid diet); a soft diet group (fed with a powder diet containing the same components as the solid one) and a molarless group (all molars were removed at 25 weeks and then fed with a powder diet). To evaluate both learning ability and memory, rats were tested with a one-way step through type of passive avoidance apparatus divided into light and dark chambers at 40-weeks. After the passive avoidance test, determination of acetylcholine (ACh) concentration of the cerebral cortex and hippocampus was performed. There was no significant difference between the molarless group and the control group in the response latency before the acquisition trails (non-stimulated period). At day 4 and 7 after the acquisition trials, the response latency of the molarless group was significantly shorter than that in the control group (p<0.05). The ACh levels of the molarless group in the cerebral cortex and hippocampus were significantly lower than that of the control group (p<0.05). It was apparent that tooth loss had an association with a loss of discriminative learning ability. This study suggested that the decrease of masticatory function caused by tooth loss leads to a decrease of ACh synthesis resulting in a learning memory disorder.     

The use of null mutant mice to study complex learning and memory processes

A number of neural substrates have been proposed to mediate complex learning and memory processes in mammalian organisms. One strategy for testing the involvement of a particular gene in learning and memory is to create a mouse line with a null mutation in that gene. Recently, embryonic stem cell-based gene-targeted homologous recombination techniques have been employed to create a number of such mutant mouse lines that do not express interesting candidate genes. These animals have been examined for impairments in several complex learning paradigms which are known to depend on the integrity of the hippocampus. In this review several complex learning and memory paradigms are described, the techniques to create null mutants are reviewed, and the results of recent studies with null mutants are described. Finally, the limitations for interpretation of behavioral data using null mutants are discussed.     

Evidence for sex-specific shifting of neural processes underlying learning and memory following stress

Recent human research has been focused upon determining whether there is evidence that stress responses cause qualitative changes in neural activity such that people change their learning strategies from a spatial/contextual memory process through the hippocampus to a procedural stimulus-response process through the caudate nucleus. Moreover, interest has shifted to determining whether males and females exhibit the same type of stress-induced change in neural processing of associations. Presented is a select review of 2 different animal models that have examined how acute or chronic stressors change learning in a sex-specific manner. This is followed by a brief review of recent human studies documenting how learning and memory functions change following stressor exposure. In both cases, it is clear that ovarian hormones have a significant influence on how stress affects learning processes in females. We then examine the evidence for a role of acetylcholine, dopamine, norepinephrine, or serotonin in modulating this shifting of processing and how that may differ across sex. Conclusions drawn suggest that there may be evidence for sex-specific changes in amygdala and hippocampus neuromodulation; however, the behavioral data are still not conclusive as to whether this represents a common or sex-specific shift in how males and females process associations after stressor exposure.     

Influence of neonatal injections of α-MSH on learning,memory and attention in rats

Three experiments were performed to assess the actions of neonatal injections of α-MSH on later behavioral testing. Experiment 1 investigated the effects of neonatal injections of α-MSH on juvenile rats' ability to learn a differential reinforcement of low rates 20 see schedule of reinforcement. The results indicated that the early treatment improved the animals' ability to respond efficiently for reinforcement. Experiment 2 assessed the effects of neonatal and adult injections of α-MSH on adult rats' ability to acquire and extinguish a two-way active avoidance response. The results indicated that treatment with α-MSH facilitated both acquisition and extinction processes. Experiment 3 studied the actions of neonatal injections of α-MSH on adult male and female rats' ability to learn a discrimination problem followed by learning a reversal problem and an extradimensional shift. The results indicated that early treatment improved performance on all three tasks for males but not females. These results were discussed in view of the methodological and procedural implications they suggested for further exploration of the actions of neuropeptides on behavior.     

The effects of the hormones of peripheral endocrine glands on the processes of behavior, learning, and memory

The effects of systemic administration of thyroid, adrenal cortex, and sex hormones on learning ability, memory trace retention, and behavior were compared in male rats. These studies showed that thyroid, corticosteroid, and sex hormones had no effect on passive learning. Excess quantities of sex hormones disrupted active learning and subsequent reproduction of received information; an excess of thyroid hormone improved the acquisition and retention of the active avoidance habit. Increases in the levels of adrenal cortex hormones worsened active learning and the retention of memory traces, and also increased the level of behavioral activity. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 48, No. 6, pp. 980–988, November–December 1998.