Post-training infusion of glutamate into the bed nucleus of the stria terminalis enhanced inhibitory avoidance memory: An effect involving norepinephrine

This study examined an interaction between glutamate and norepinephrine in the bed nucleus of the stria terminalis (BNST) in modulating affective memory formation. Male Wistar rats with indwelling cannulae in the BNST were trained on a one-trial step-through inhibitory avoidance task and received pre- or post-training intra-BNST infusion of glutamate, norepinephrine or their antagonists. Results of the 1-day test indicated that post-training intra-BNST infusion of dl-2-amino-5-phosphonovaleric acid (APV) impaired retention in a dose- and time-dependent manner, while infusion of glutamate had an opposite effect. Co-infusion of 0.2 μg glutamate and 0.02 μg norepinephrine resulted in marked retention enhancement by summating non-apparent effects of the two drugs given at a sub-enhancing dose. The amnesic effect of 5.0 μg APV was ameliorated by 0.02 μg norepinephrine, while the memory enhancing effect of 1.0 μg glutamate was attenuated by 5.0 μg propranolol. These findings suggest that training on an inhibitory avoidance task may alter glutamate neurotransmission, which by activating NMDA receptors releases norepinephrine to modulate memory formation via β adrenoceptors in the BNST.     

治疗糖尿病创新药物研究

本论文从治疗2型糖尿病药物应用现状出发,通过对2型糖尿病病理的认识,新发现的主要受体和相关药靶等方面进行分析。指出随着对糖尿病认识的深入发展,治疗糖尿病创新药物研究的发展趋势也发生了相应的变化,就是从局部治疗到全身综合考虑,从药物外部直接地干预到增强自身调节功能。为治疗2-型糖尿病药物发展指明了方向。     

鼻咽癌组织VEGF、TNF—α及其受体VEGFR1、P55的表达及意义

观察鼻咽癌黏膜上皮中血管内皮生长因子（VEGF）、肿瘤坏死因子α（TNF—α）及受体血管生长因子1（VEGFR1）,肿瘤坏死生长因子受体蛋白55（P55）的表达情况,探讨其在鼻咽癌发病及进展中的意义。我们应用免疫组化SP法检测60例鼻咽癌和60例正常鼻黏膜上皮组织VEGF、TNF—α及VEGFR1、P55表达情况,分析其在鼻咽癌组织中的表达变化及意义。结果显示鼻咽癌黏膜上皮的VEGF、TNF—α、VEGFR1、P55表达高于正常鼻黏膜上皮。因此VEGF、TNF—α及其受体VEGFR1、P55在鼻咽癌黏膜上皮中过度表达,可能参与鼻咽癌的发病及疾病进展,对于鼻咽癌的预防及治疗具有重要意义。     

Antiaggressive Effects of Zolpidem and Zopiclone in Agonistic Encounters Between Male Mice

The effects of benzodiazepines on various types of aggression have been extensively studied. These substances produce their pharmacological effects by allosterically modulating the action of GABA via specific recognition sites on the GABA_A receptor called omega 1 and omega 2. The antiaggressive profile of non‐benzodiazepine compounds that also act at omega sites, such as zopiclone (a non‐selective omega 1 and 2 ligand) and zolpidem (a selective omega 1 ligand) has been scarcely explored. In this study, we examined the action of zolpidem (0.75‐3 mg/kg, intraperitoneally) and zopiclone (1.5‐6 mg/kg), administered acutely or subchronically for 10 days, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with zopiclone produced a marked antiaggressive effect, reducing offensive behaviors (threat and attack) at all doses used (1.5, 3, and 6 mg/kg) without affecting immobility. Likewise, the intermediate dose of zolpidem (1.5 mg/kg) significantly decreased aggression in a specific manner, without altering immobility, whereas the highest dose (3 mg/kg) provoked a reduction of aggression accompanied by a weak (but significant) increase of immobility. With repeated treatment, no tolerance to the antiaggressive effects of zopiclone and zolpidem was developed. It is concluded that omega sites at the GABA_A receptor could be involved in the control of aggression. Aggr. Behav. 28:416–425, 2002. © 2002 Wiley‐Liss, Inc.     

催产素及受体基因与社会适应行为

作为一种在哺乳动物分娩和泌乳中起神经调节作用的激素, 催产素(oxytocin, OT)在人类的母婴关系和社会关系中也发挥着重要作用。研究发现催产素及其受体基因与人类的社会适应行为关系密切。催产素会影响亲子依恋和父母教养行为, 也能促进人际信任及慷慨行为; 同时, 不同催产素受体(oxytocin receptor, OXTR)基因型的个体, 在亲子关系和一些亲社会行为方面都表现出了差异。来自于激素和基因水平的研究提示我们, 催产素及其受体基因可能是通过促进社会识别、调节共情以及降低恐惧、减缓焦虑来影响人类一系列的社会适应行为。未来的研究应考虑结合分子遗传学和神经科学的研究方法, 从基因－激素－行为三个层面系统的研究催产素影响社会行为的分子过程和认知神经过程。     

The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice

Oroxylin A is a flavonoid and was originally isolated from the root of Scutellaria baicalensis Georgi., one of the most important medicinal herbs in traditional Chinese medicine. The aim of this study was to investigate the ameliorating effects of oroxylin A on memory impairment using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by administering scopolamine (1 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Oroxylin A (5 mg/kg) significantly reversed cognitive impairments in mice by passive avoidance and the Y-maze testing (P<.05). Oroxylin A also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P<.05). Moreover, the ameliorating effects of oroxylin A were antagonized by both muscimol and diazepam (0.25 mg/kg, i.p., respectively), which are GABA(A) receptor agonists. Furthermore, oroxylin A (100 microM) was found to inhibit GABA-induced inward Cl(-) current in a single cortical neuron. These results suggest that oroxylin A may be useful for the treatment of cognitive impairments induced by cholinergic dysfunction via the GABAergic nervous system.     

Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning

Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400 microg/ml) in their drinking water (days 1-21), a manipulation that was previously shown to cause hippocampal CA3 dendritic retraction. Subsequently, rats were adapted to the fear conditioning chamber (day 22), then trained (day 23), and tested for conditioned fear to context and tone (day 25). Training consisted of two tone (20s) and footshock (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 microl/side), a GABAergic agonist, was microinfused to temporarily inactivate the BLA during training. Rats given chronic corticosterone showed enhanced freezing to context, but not tone, compared to vehicle-supplemented rats. Moreover, BLA inactivation impaired contextual and tone conditioning, regardless of corticosterone treatment. In Experiment 2, RU486 (0, 0.3, and 3.0 ng/0.2 microl/side) was infused on training day to antagonize glucocorticoid receptors in the BLA. Corticosterone treatment enhanced fear conditioning to context and tone when analyzed together, but not separately. Moreover, RU486 (3.0 ng/side) selectively exacerbated freezing to context in chronic corticosterone-exposed rats only, but failed to alter tone conditioning. Serum corticosterone levels were negatively correlated with contextual, not tone, conditioning. Altogether, these suggest that chronic corticosterone influences fear conditioning differently than chronic stress as shown previously. Moreover, chronic exposure to corticosteroids alters BLA functioning in a non-linear fashion and that contextual conditioning is influenced more than tone conditioning by chronic corticosterone and BLA glucocorticoid receptor stimulation.     

Bicuculline infusion into the accessory olfactory bulb facilitates the induction of maternal behavior in rats

The GABAA antagonist bicuculline, intracranially infused into the accessory olfactory bulb (AOB), facilitated the expression of maternal behavior (MB) in virgin Wistar female rats. Behavioral effects were observed 24 hours after infusion and were injection dependent. Pheromonal stimuli, generated by the pups, are thought to exert an inhibitory effect on vomeronasal nuclei involved in MB in virgin rats. The present study investigated the possibility that a decrement in AOB output, resulting from long-term compensatory synaptic changes to chronic bicuculline infusion, would facilitate the expression of MB. The implications of our findings for the mechanisms involved in the induction of MB and the maternal experience effect are discussed.     

Cognitive Reliability of the Sense of Touch Confronted with the Thinning Effect

The dependence of the cognitive function of the sense of touch of the area sensorium was investigated by means of the thinning illusion produced by rotating the cylindrical rod between the thumb and the forefinger. The genetic phases of this illusion were traced from sensations to perceptions and to meaningful cognition converting the rod's objective convexity into an apparent concavity, running seemingly around the rod. Adult subjects (N = 52) experimentally checked all variables on their optimum degree for producing this illusion, which showed an effective way for using illusions for a thorough investigation of mental synthetic processes.