Characterization of quinolone antibacterial-induced convulsions and increases in nuclear AP-1 DNA- and CRE-binding activities in mouse brain.

The quinolone antibacterials enoxacin and norfloxacin (2.5 mg/kg, i.v.) provoked clonic convulsions in mice treated concomitantly with biphenylacetic acid (BPAA, 100 mg/kg, i.p.), a major metabolite of the nonsteroidal anti-inflammatory drug fenbufen. Gel-shift assays showed that enoxacin-induced convulsions resulted in increases in nuclear activator protein 1 (AP-1) DNA- and cyclic AMP responsive element (CRE)-binding activities in the cerebral cortex and hippocampus, but not in other regions, such as the cerebellum and thalamus. In contrast, ofloxacin and levofloxacin, at the same doses, in the presence of BPAA did not evoke convulsions or increase these DNA-binding activities. Administration of these quinolones and BPAA alone elicited neither convulsions nor increases in these DNA-binding activities. These results suggest that the increased nuclear AP-1 DNA- and CRE-binding activities in the cerebral cortex and hippocampus induced by quinolones with BPAA correlated with seizure activities and that these brain regions play pivotal roles in quinolone-induced convulsions.     

Brain IL-1 beta was involved in reserpine-induced behavioral depression in rats.

AIM: To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS: Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS: Intraperitoneal injection of reserpine (0, 4, 6, and 8 mg/kg, ip) increased floating time in the Porsult swim test in a dose-and time-dependent manner in rats. Intracerebroventricular injection (icv) of IL-1 beta receptor antagonist (IL-1ra, 6 mg/kg) blocked the increment of floating time in Porsult swim test at 48 and 72 h after reserpine injection, but not at 1 and 24 h after injection. Brain IL-1 beta increased after reserpine treatment in posterior cortex, hippocampus, and hypothalamus. The increase of IL-1 beta concentration starts at 24 hours after injection of reserpine and reached the peak at 48 h. CONCLUSION: Reserpine induced behavioral depression partially via brain interleukin-1 beta generation.     

人参皂苷Rg1对慢性应激抑郁模型大鼠谷氨酸及其受体表达的影响

目的：观察人参皂苷Rg1对慢性应激抑郁模型大鼠脑内海马、前额叶皮质区谷氨酸及其不同类型受体表达的影响，探讨其潜在的抗抑郁机制。方法：将SD大鼠随机分为5组：正常组、模型组、氟西汀组（10 mg·kg^-1）、人参皂苷Rg1低、高剂量组（25、50 mg·kg^-1）。采用慢性不可预见性温和应激的方法建立抑郁大鼠模型，于造模同时灌胃给药，共21天。造模结束后采用Morris水迷宫和旷场实验评价大鼠的抑郁样行为，HE染色观察大鼠海马、前额叶皮质区病理改变情况，HPLC法检测谷氨酸含量，Western-blotting法检测离子型谷氨酸受体NMDAR1、代谢型谷氨酸受体mGluR1的蛋白表达情况。结果：与正常组比较，模型组大鼠抑郁样行为显著，海马、前额叶皮质区均存在较为明显的损伤，谷氨酸含量显著升高，NMDAR1、mGluR1蛋白表达均显著上调；在给予人参皂苷Rg1干预后，模型大鼠的抑郁样行为得到缓解，海马、前额叶皮质区损伤减轻，谷氨酸含量下降，NMDAR1、mGluR1蛋白表达水平明显逆转。结论：人参皂苷Rg1对大鼠抑郁症状有明显的改善作用，并能减轻海马和前额叶皮质损伤，其机制可能与调节脑内谷氨酸含量，并抑制其受体表达有关。     

Selective increases in the cytokine, TNFalpha, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs

The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF 1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.     

皮质前额叶和海马PPAR-α通路参与N-棕榈酰乙醇胺抗大鼠抑郁样行为

目的　探讨皮质前额叶（PFC）和海马中α型过氧化物酶体增殖物激活受体（PPARα）参与N-棕榈酰乙醇胺（PEA）调控慢性应激诱导大鼠抑郁样行为的机制。方法　将50只SD大鼠按照随机数字表法分为正常对照组、模型组、氟西汀组（阳性药物对照,10 mg/kg）、PEA组（10 mg/kg）和PEA+MK886组（PEA 10 mg/kg+MK886 3 mg/kg）,每组10只。除正常对照组外,其余各组大鼠给予慢性不可预见性温和应激（CUMS）和孤养应激干预4周建立抑郁模型,建模1周时分组给予相应药物干预4周。第36天麻醉大鼠后取脑组织标本,通过免疫组化染色观察皮质前额叶（PFC）和海马中多唾液酸-神经细胞黏附分子（PSA-NCAM）蛋白表达情况;酶联免疫吸附试验（ELISA）检测大鼠PFC中脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）的表达,及PFC和海马中肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）和核转录因子-κB（NF-κB）的水平。结果　PEA上调了CUMS抑郁模型大鼠PFC和海马中PSA-NCAM及PFC中BDNF和GDNF蛋白表达,下调了PFC和海马中TNF-α、IL-1β和NF-κB水平。与PEA组相比,PEA+MK886组大鼠PFC和海马中PSA-NCAM、PFC中BDNF和GDNF的表达下调,PFC和海马中TNF-α、IL-1β、NF-κB的水平增加。结论　PEA可通过调控PFC和海马的PPARα通路促进神经可塑性、缓解神经炎症,发挥神经保护作用,从而改善CUMS大鼠的抑郁样行为。     

Effect of prior stress on interleukin-1β and HPA axis responses to acute stress

Interleukin-1β (IL-1β) level is modulated during multiple stress reactions both in brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1β and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1β levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA axis responses. Experiments were performed on male Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days. Twenty four hours after the last stress period rats were restrained for 10 min and decapitated at 0, 1, 2 or 3 h after cessation of stress. Control rats were injected ip with saline and some of experimental groups with IL-1β receptor antagonist (IL-1ra). After rapid decapitation, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Interleukin-1β, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined in plasma using commercially available kits and IL-1β levels in brain structures samples were analyzed by western blot procedure. Repeated restraint for 3 days alone did not alter resting plasma levels of IL-1β, and moderately augmented plasma ACTH and CORT levels and IL-1β content in brain structures 24 h after the last restraint. IL-1β antagonist abolished the increase in plasma levels of IL-1β, ACTH and CORT as well as IL-1β in brain structures in response to repeated stress and also reduced these changes induced by 10 min stress. This suggests the selectivity of IL-1β receptors in central and peripheral mechanisms modulating the stress-induced HPA axis responses. These results indicate that repeated stress markedly increases IL-1β production in brain structures involved in HPA axis regulation. The present results support the role of brain and peripheral IL-1β in adaptation of HPA response during prolonged stress.     

Effect of repeated restraint on homotypic stress-induced nitric oxide synthases expression in brain structures regulating HPA axis

BackgroundRestraint stress (RS) markedly increases interleukin 1-β (IL-1β) generation in brain structures involved in hypothalamic-pituitary adrenocortical (HPA) axis regulation. The IL-1β-induced transient stimulation of HPA axis activity was parallel in time and magnitude to respective changes in regulation of HPA activity. In the present experiment the expression of neuron al and inducible nitric oxide synthase (nNOS and iNOS) were investigated in prefrontal cortex, hippocampus and hypothalamus in response to acute restraint stress in control and prior repeatedly restrained rats.MethodsExperiments were performed on male Wistar rats which were exposed to 10 min restraint stress or restrained twice a day for 3 days, and 24 h after the last stress period exposed to homotypic stress for 10 min. After rapid decapitation at 0,1,2 and 3 h after cessation of stress, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Interleukin-1β, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined in plasma using commercially available kits and neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in brain structure samples were analyzed by western blot procedure.ResultsPrior repeated restraint stress enhanced the acute restraint stress induced increase in IL-1β levels in all three structures examined. Restraint stress for 10 min moderately decreased nNOS level in prefrontal cortex in control rats, augmented this level in hippocampus and markedly increased nNOS level in hypothalamus. Restraint itself significantly decreased iNOS level in prefrontal cortex, while it enhanced iNOS level in hippocampus and hypothalamus. Prior restraint stress for 3 days enhanced the nNOS level in prefrontal cortex and hippocampus and did not substantially affect nNOS levels response in hypothalamus. Repeated restraint stress considerably augmented the iNOS levels in both prefrontal cortex, hippocampus and hypothalamus induced by followed homotypic stress.ConclusionThese results indicate that during restraint stress nNOS regulate formation of low amount of NO and the high-output generation of NO is effected by inducible isoform of nitric oxide synthase. Prior repeated stress significantly enhances the homotypic stress-induced nNOS and iNOS responses.     

Changes in neurotransmitter levels and proinflammatory cytokine mRNA expressions in the mice olfactory bulb following nanoparticle exposure

Recently, there have been increasing reports that nano-sized component of particulate matter can reach the brain and may be associated with neurodegenerative diseases. Previously, our laboratory has studied the effect of intranasal instillation of nano-sized carbon black (CB) (14 nm and 95 nm) on brain cytokine and chemokine mRNA expressions and found that 14-nm CB increased IL-1 beta, TNF-alpha, CCL2 and CCL3 mRNA expressions in the olfactory bulb, not in the hippocampus of mice. To investigate the effect of a single administration of nanoparticles on neurotransmitters and proinflammatory cytokines in a mouse olfactory bulb, we performed in vivo microdialysis and real-time PCR methods. Ten-week-old male BALB/c mice were implanted with guide cannula in the right olfactory bulb and, 1 week later, were instilled vehicle or CB (14 nm, 250 microg) intranasally. Six hours after the nanoparticle instillation, the mice were intraperitoneally injected with normal saline or 50 mug of bacteria cell wall component lipoteichoic acid (LTA), which may potentiate CB-induced neurologic effect. Extracellular glutamate and glycine levels were significantly increased in the olfactory bulb of CB-instilled mice when compared with vehicle-instilled control mice. Moreover, we found that LTA further increased glutamate and glycine levels. However, no alteration of taurine and GABA levels was observed in the olfactory bulb of the same mice. We also detected immunological changes in the olfactory bulb 11 h after vehicle or CB instillation and found that IL-1 beta mRNA expression was significantly increased in CB- and LTA-treated mice when compared with control group. However, TNF-alpha mRNA expression was increased significantly in CB- and saline-treated mice when compared with control group. These findings suggest that nanoparticle CB may modulate the extracellular amino acid neurotransmitter levels and proinflammatory cytokine IL-1 beta mRNA expressions synergistically with LTA in the mice olfactory bulb.     

Dynamic modulation of basic Fibroblast Growth Factor (FGF-2) expression in the rat brain following repeated exposure to cocaine during adolescence

Rationale

Our study stems from four related lines of evidence: (1) FGF-2 is expressed in the developing brain; (2) psychostimulants modulate FGF-2 expression; (3) stress alters FGF-2 expression; and (4) exogenous administration of FGF-2 long-lastingly alters cocaine acquisition of self-administration.

Objectives

This research aims to study the effects of adolescent cocaine exposure on FGF-2 mRNA levels and its influence on the response to stress.

Materials and methods

Rats were treated subcutaneously with saline or cocaine from postnatal day (PND) 28 to PND 42, a period that roughly approximates adolescence in humans. At PND 45 and PND 90, rats were exposed to an acute stress. Real-time PCRs were performed on total RNA extracted from the prefrontal cortex, hippocampus, nucleus accumbens and striatum.

Results

In the prefrontal cortex, repeated cocaine treatment during adolescence increased FGF-2 mRNA levels in PND 90 rats and altered its response to an acute stress in both PND 45 and PND 90 rats. In the hippocampus of PND 45 rats, we found an increase of FGF-2 mRNA levels following repeated cocaine administration. No changes in the trophic factor gene expression were found in the striatum and nucleus accumbens.

Conclusions

Our data show that cocaine exposure during adolescence alters FGF-2 mRNA levels throughout life in rat prefrontal cortex and modulates its response to an adverse event. These results point to FGF-2 as a potential molecular target through which exposure to cocaine early in life may dynamically and persistently alter brain homeostasis.     

Changes in regional brain acetylcholine levels during drug-induced convulsions

Acetylcholine (ACh) levels were determined in the brain of rats killed by decapitation or focussed microwave radiation during drug-induced convulsions. During metrazol or strychnine-induced convulsions a diffuse decrease in ACh levels was found in rats killed by decapitation. When the rats were killed by radiation and the brain was only divided into three large regions, strychnine caused no changes in ACh levels; metrazol caused a decrease in the cerebral cortex and lower brainstem. When discrete brain regions were investigated in rats killed by radiation, metrazol-induced convulsions were associated with a decrease in ACh level in all regions dissected and strychnine-induced convulsions with a decrease in the hippocampus and caudate nucleus only. Picrotoxin-induced convulsions were associated with a decrease in ACh level in the cerebral cortex, hippocampus, midbrain and medullapons, those induced by bicuculline with an increase in ACh level in the frontal cortex, hippocampus, midbrain and medulla-pons, by dimefline with an increase in the frontal cortex, midbrain and medulla-pons and a decrease in the caudate nucleus. The experiments show that each type of convulsant affects ACh levels in discrete brain regions in a different way.     

Soman-induced convulsions affect the inositol lipid signaling system: potentiation by lithium; attenuation by atropine and diazepam

Effects of atropine or diazepam pretreatment on soman-induced convulsions and brain phosphoinositide (PI) metabolism, as assessed by brain regional inositol-1-phosphate (IP1) levels, were studied in saline and LiCl-pretreated rats. IP1, an intermediate in PI turnover, was measured in cortex, caudate, thalamus, hippocampus, and cerebellum. Soman (100 micrograms/kg; sc) produced convulsions in 63% of the saline-pretreated rats, whereas with LiCl pretreatment all rats exposed to 100 micrograms/kg of soman had tonic-clonic convulsions. Thus, LiCl pretreatment potentiated soman-induced convulsions. Tissue IP1 increased severalfold in soman-exposed convulsing rats with the highest increases being in frontal cortex and caudate. In contrast, no marked increases of IP1 occurred in similarly treated nonconvulsing rats. LiCl treatment itself increased IP1 levels without causing convulsions. In LiCl-pretreated rats, soman again markedly elevated IP1 levels above LiCl alone in convulsing rats, whereas no such effect occurred in nonconvulsing rats. In LiCl-pretreated rats, the increased IP1 levels associated with soman-induced convulsions were greatest in hippocampus and piriform cortex. Thus, LiCl appears to lower the threshold for the spread of seizure activity through limbic structures, thereby potentiating cholinergic-induced convulsions. Diazepam and atropine both blocked soman-induced convulsions, and brain regional IP1 elevations were concomitantly abolished as well. These results indicate that soman-induced convulsions involve the inositol lipid signaling system. This involvement is potentiated by lithium but attenuated by atropine and diazepam.     

Pharmacological evaluation of garenoxacin,a novel des-F(6)-quinolone antimicrobial agent: effects on the central nervous system

The effects of garenoxacin (formerly T-3811 or BMS-284756) on the central nervous system (CNS) were compared with various quinolones. Garenoxacin injected intracerebroventricularly into mice caused clonic convulsion at a higher dose (50 micrograms/body) than norfloxacin, ciprofloxacin, sitafloxacin and trovafloxacin. Additionally the convulsant activity of garenoxacin was not potentiated by biphenylacetic acid (BPAA). Garenoxacin did not induce any convulsions at intravenous doses up to 60 mg/kg in combination with 200 mg/kg oral administration of fenbufen in mice, and its convulsant activity was weaker than those of enoxacin, norfloxacin, ciprofloxacin, alatrofloxacin and ofloxacin. In addition, convulsions were not induced by combination administration of garenoxacin (60 mg/kg, i.v.) and any of 9 kinds of nonsteroidal anti-inflammatory drugs (NSAIDs) or BPAA. In a rotarod test, which was performed in order to evaluate the drug-induced dizziness, coordinated locomotor activity of mice was suppressed by alatrofloxacin at an intravenous dose of 60 mg/kg, but not by garenoxacin, ciprofloxacin and norfloxacin at up to 60 mg/kg. In an in vitro study using rat brain synaptic membrane, garenoxacin had no inhibitory effect on GABA binding in the presence or absence of NSAIDs. In conclusion, the effects of garenoxacin on CNS were weaker than those of other quinolones in experimental animals, so it might possess a low potential for CNS adverse reactions such as convulsion and dizziness in clinical use.     

GABAA receptor subunit mRNA levels are differentially influenced by chronic FG 7142 and diazepam exposure.

Levels of mRNA for the alpha 1, gamma 2 and beta 1 subunits of the GABAA receptor complex were examined in rats maintained on a chronic, continuous schedule of exposure to the benzodiazepine inverse agonist FG 7142. The effect of chronic exposure to the benzodiazepine agonist diazepam was also examined on levels of gamma 2 subunit mRNA. FG 7142 (2 mg/ml of 100% dimethyl sulfoxide (DMSO) or vehicle (100% DMSO) was administered continuously for 8 days in the right ventricle via an osmotic minipump. At the end of the eighth day of exposure, the brain was removed and cerebral cortex, cerebellum and hippocampus were dissected and mRNA prepared from each region. Levels of GABAA alpha 1 and gamma 2 subunit mRNA were examined by Northern blot analysis with cDNA probes specific for these subunits. A significant increase in alpha 1 mRNA was measured in both cortex and hippocampus, but not in cerebellum, of rats chronically exposed to FG 7142 relative to vehicle-treated rats. A significant increase in gamma 2 subunit mRNA in cortex was also evident in drug-treated rats; however, no change in gamma 2 subunit mRNA was observed in either the hippocampus or cerebellum. Examination of GABAA beta 1 subunit mRNA by solution hybridization using a beta 1 riboprobe revealed no effect of chronic FG 7142 treatment on this subunit in either cortex, hippocampus or cerebellum. In rats chronically exposed to diazepam (21 days via silastic implants), levels of gamma 2 subunit mRNA were significantly decreased in cortex, but not changed in either hippocampus or cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biphenylacetic acid enhances the antagonistic action of fluoroquinolones on the GABA(A)-mediated responses of the isolated guinea-pig ileum.

This paper examines the effect of biphenylacetic acid on the antagonistic action of norfloxacin and enoxacin on the GABA(A)-mediated responses of the isolated guinea-pig ileum. GABA produced transient contractions followed by relaxation. The contractile effect of exogenously applied GABA was concentration-dependent with EC(50)= 9.8 x 10(-6) M. This contractile effect was not significantly modified by biphenylacetic acid, and the EC(50) value for GABA in the presence of 10(-5) M biphenylacetic acid was 1.15 x 10(-5) M. The GABA contractile effect was inhibited, dose-dependently, by either norfloxacin or enoxacin, but only at concentrations higher than 10(-5) M. The response of the ileum to GABA (at EC(50)) was reduced to 35 and 36% by pretreatment with 10(-5) M norfloxacin or enoxacin, respectively. However, in the presence of 10(-5) M biphenylacetic acid, the response of the ileum to GABA was reduced to 2.2% by pretreatment with 10(-5) M enoxacin, while it was completely abolished by pretreatment with 10(-5) M norfloxacin and the IC(50) values were 5.5 x 10(-7) and 1.5 x 10(-6) M for norfloxacin and enoxacin, respectively. These data show that biphenylacetic acid whilst having no effect at the GABA(A)-mediated contractile response of the guinea-pig ileum, enhances the antagonistic effect of both enoxacin and norfloxacin. This suggests that combined administration of fluoroquinolones and biphenylacetic acid synergistically inhibits GABA(A)-receptors at the intestinal level.     

Delta9-tetrahydrocannabinol enhances cortical and hippocampal acetylcholine release in vivo: a microdialysis study.

The intravenous administration of synthetic cannabinoid agonists was recently shown to dose dependently increase acetylcholine release from the rat prefrontal cortex and hippocampus (Eur. J. Pharmacol. 401 (2000) 179]. We report here that the active ingredient of cannabis preparations, delta9-tetrahydrocannabinol, administered at 10, 37.5, 75 and 150 microg/kg, dose dependently stimulated acetylcholine release from rat prefrontal cortex and hippocampus estimated by means of in vivo brain microdialysis with vertical concentric probes. At these doses, delta9-tetrahydrocannabinol induced behavioural stimulation. The administration of the CB1 receptor antagonist, ([N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3carboxamide]HCl) SR 141716A (200 microg/kg i.p.) significantly reduced the effect of delta9-tetrahydrocannabinol (75 microg/kg i.v.) on acetylcholine release from rat prefrontal cortex and hippocampus.     

银杏叶提取物对U937泡沫细胞IL-1β、TNF-α及IL-10表达的影响

本研究考察了氧化低密度脂蛋白(ox-LDL)刺激的U937细胞致炎细胞因子白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、抗炎细胞因子白细胞介素10(IL-10)及其受体(IL-10R)的蛋白及mRNA的表达，同时观察银杏叶提取物(GbE)对它们的作用。U937细胞用100 mg·L^-1 ox-LDL刺激24 h形成泡沫细胞，同时分别加入不同浓度的GbE(0.1, 1及10 μg·L^-1)共孵育，采用酶联免疫吸附试验(ELISA)及逆转录聚合酶链式反应(RT-PCR)方法检测IL-1β、TNF-α、IL-10和IL-10R的蛋白或mRNA表达。U937泡沫细胞组IL-1β、TNF-α、IL-10和IL-10R的蛋白或mRNA的表达较对照组显著增加(P<0.01)。GbE组IL-1β及TNF-α的蛋白和mRNA的表达水平明显降低，IL-10的蛋白、IL-10和IL-10R的mRNA表达水平明显提高，与U937泡沫细胞组相比差异显著(P<0.05, P<0.01)。GbE对U937泡沫细胞致炎细胞因子IL-1β及TNF-α表达的显著抑制作用，对抗炎细胞因子IL-10及其受体IL-10R表达的显著上调作用可能是其抗atherosclerosis(AS)的机制之一。     

The effects of isolation rearing on glutamate receptor NMDAR1A mRNA expression determined by in situ hybridization in Fawn hooded and Wistar rats

Rats reared in social isolation exhibit a syndrome of behavioral and biochemical effects indicative of enhanced mesolimbic dopamine (DA) function. The precise nature of the neurodevelopmental changes that produce this state are unknown but result in enhanced DA neurotransmission in the nucleus accumbens (NAC). It was hypothesized that this may be the indirect result of chronic changes in glutamate NMDA receptor function. The same prediction has been made for Fawn hooded (FH) rats that exhibit some of the characteristic effects of isolation-reared rats when compared to Wistar rats. Therefore, mRNA levels of the NMDAR1A receptor subunit were determined by in situ hybridization and were quantified in the striatum, hippocampus and prefrontal cortex of FH and Wistar rats. Isolation rearing alone was not found to have an effect on the expression of NMDAR1A, while FH rats had reduced levels across most brain regions examined. In some areas of the striatum and prefrontal cortex, this effect was greater in FH isolates than in FH socials, while in the hippocampus, the opposite was observed.     

大脑中动脉栓塞模型大鼠的中枢电压依赖性钾通道mRNA表达的改变

目的观察几种代表性电压依赖性钾通道亚型在脑缺血不同时间大鼠海马和皮层mRNA表达水平的变化。方法采用大脑中动脉栓塞模型致大鼠脑缺血损伤，应用RT-PCR方法检测Kv1.4，Kv1.5，Kv2.1和Kv4.2 mRNA表达水平在海马和皮层中的改变。结果大脑中动脉栓塞模型大鼠出现明显的神经损伤症状。缺血2 h时，海马组织的Kv1.4，Kv2.1和Kv4.2 mRNA表达水平分别增加了50%，67%和90%，在缺血24 h时Kv1.4和Kv4.2 mRNA仍保持高水平表达。大鼠皮层组织在缺血2 h后，Kv1.4，Kv1.5，Kv2.1和Kv4.2 mRNA水平均无明显改变，缺血24 h后，Kv2.1和Kv4.2 mRNA水平分别增加了70%和62%。结论大脑中动脉栓塞模型大鼠的海马和皮层组织中电压依赖性钾通道亚型的mRNA表达发生明显上调。