The nitric oxide-guanosine 3',5'-cyclic monophosphate pathway regulates dopamine efflux in the medial preoptic area and copulation in male rats

Dopamine in the medial preoptic area (MPOA) plays a significant role in regulation of male copulation. One mediator of the MPOA dopamine level is nitric oxide. In the current study, we investigated the role of the nitric oxide-guanosine 3',5'-cyclic monophosphate (cGMP) pathway in the regulation of MPOA dopamine and copulation in male rats. The reverse-dialysis of a membrane-permeable analog, 8-Br-cGMP, increased, while a soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), significantly reduced basal dopamine and its metabolite levels. ODQ successfully blocked a nitric oxide donor-induced increase in dopamine levels, while a neuronal nitric oxide synthase (nNOS) inhibitor was ineffective in blocking an 8-Br-cGMP-induced increase in dopamine, indicating that cGMP is "downstream" of nitric oxide. Furthermore, 8-Br-cGMP facilitated, while ODQ inhibited copulation. Given the steroid-sensitive nature of nNOS functions and the multiple roles nitric oxide plays in the MPOA, we propose that nitric oxide provides important integration of various neurochemical and neuroendocrine signals. The involvement of the central nitric oxide-cGMP pathway in the regulation of copulation also raises an interesting therapeutic possibility, as the manipulation of the same pathway in peripheral tissue is already utilized in treatment of male sexual dysfunction.     

天然抗氧化剂减少神经根撕脱诱导的一氧化氮合酶表达和运动神经元死亡

为了研究抗老年性痴呆 990 1号和 TA990 1+银杏叶标准提取物合剂对臂丛神经根撕脱后前角运动神经元的神经元型一氧化氮合酶 ( n NOS)表达和存活的影响 ,用成年 SD雌性大鼠进行右侧臂丛 C5～ T1 神经根撕脱术后 ,随机分为撕脱组、撕脱 +TA990 1组以及撕脱 +TA990 1和 EGb761合剂组。对此三组每天分别进行腹腔注射 1ml生理盐水、0 .5 % TA990 1、0 .5 %TA990 1和 EGb761合剂。治疗 5 d、1、2、4和 6周后处死动物并进行 NADPH-d染色及中性红复染。定量比较各组 n NOS阳性和存活的运动神经元数量。结果证明 ,神经根撕脱后 5 d受损运动神经元开始表达 n NOS,2周时达高峰 ,随后下降至 6周。受损运动神经元的死亡从 2周开始 ,4～ 6周最明显。抗氧化剂治疗组 n NOS表达规律与对照组相似 ,但是阳性程度和阳性细胞数量均少于对照组 ,存活的运动神经元数量则明显多于对照组。撕脱后 4～ 6周 ,TA990 1治疗组抑制 n NOS表达和提高运动神经元存活的效果均明显优于 TA990 1和 EGb761合剂组。结论 :天然抗氧化剂可有效地减少臂丛神经根撕脱后 n NOS表达 ,提高受损运动神经元的存活。 TA990 1抑制 n NOS表达的作用强于 EGb761。     

Dopamine D1 receptors and phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in the medial preoptic area are involved in experience-induced enhancement of male sexual behavior in rats

The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D? receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In experiment 1, microinjections of the D? antagonist SCH-23390 into the MPOA before each of seven daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on Day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to that of vehicle-treated males that had not been preexposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D? receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and na?ve controls. These data suggest that D? receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism.     

Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats

We have recently found that a combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and that estrogen replacement suppresses the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of Ginkgo biloba extract (EGb 761), a popular herbal supplement, on the cognitive dysfunction and neuromorphological change in OVX/stress-subjected rats. Female Fisher 344 rats were randomly divided into three groups: vehicle-treated OVX, EGb 761 (50 mg/kg) -treated OVX and vehicle-treated sham-operated control groups. Two months after ovariectomy, all animals received restraint stress for 21 days (6 h/day), and were then subjected to a novel object recognition test followed by morphological examination by Nissl staining. EGb 761 was orally administered once daily until the behavioral analysis was done. Treatment with EGb 761 improved memory impairment and neuronal loss of hippocampus in the OVX/stress-subjected group in the same ways as 17beta-estradiol. On the other hand, EGb 761 did not affect the loss of bone mineral density and increase in body weight after OVX, although 17beta-estradiol attenuated them. These results have important implications for neuroprotective and cognition enhancing effects of EGb 761 in postmenopausal women and suggest that the effects are mediated by a different mechanism from estrogen.     

iNOS expression in rat aorta is increased after spinal cord transection: a possible cause of orthostatic hypotension in man

Orthostatic hypotension commonly occurs in persons with spinal cord injury (SCI), limiting rehabilitation and independence. Findings of increased production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) after exposure to simulated microgravity suggest that increased iNOS expression contributes to OH in persons with SCI. To test this possibility, male Wistar rats underwent surgical transection of the spinal cord (T10) or sham-SCI surgery followed by euthanasia 3, 7 or 14 days later. Expression in thoracic aortic of inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NOS was then determined. In SCI rats, expression of iNOS mRNA was decreased at 3 days, had returned to normal levels of expression at 7 days and was increased at 14 days post-SCI (1.8-fold). In contrast, levels of eNOS mRNA were increased at 3 days (1.4-fold), then declined over time reaching levels by day 14 that were reduced compared to sham-SCI (0.23-fold). There were no significant effects of SCI on nNOS expression. These findings suggest a possible role for increased iNOS expression in the pathogenesis of OH in persons with SCI.     

A nitric oxide synthesis inhibitor in the medial preoptic area inhibits copulation and stimulus sensitization in male rats

Dopamine in the medial preoptic area (MPOA) facilitates copulation in male rats, and nitric oxide (NO) regulates basal and female-stimulated MPOA dopamine release. Microinjection of L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor) into the MPOA blocked copulation in naive rats and impaired copulation in sexually experienced males. In other naive rats, L-NAME or saline was microinjected into the MPOA before each of 7 daily exposures to a receptive female placed over their cage. In a drug-free test on Day 8, copulation by L-NAME-treated rats was similar to that of unexposed controls and was impaired relative to saline-treated males. Therefore, NO in the MPOA is important for copulation and stimulus sensitization in male rats.     

银杏叶提取物联合盐酸文拉法辛对抑郁大鼠海马nNOS蛋白表达及NO水平的影响

目的 :探讨抑郁症脑损伤的机制 ,研究银杏叶提取物 (EGb)及合成抗抑郁药盐酸文拉法辛(Venlafaxine)对抑郁大鼠的抗脑损伤及神经元保护作用。方法 :慢性应激建立大鼠抑郁模型。将 84只雄性大鼠分为正常对照组、抑郁模型组和不同治疗组。快速断头法处死 ,取海马后一侧进行免疫组化反应 ,观察海马CA3区nNOS蛋白的表达 ;另一侧检测NO含量 ;同时测定血清中NO含量。结果 :抑郁模型组海马nNOS表达增加 ,海马及血清中NO含量增加 ,P <0 0 1;联合用药组海马nNOS表达下降 ,海马及血清中NO含量减少 ,P <0 0 1。结论 :慢性应激增加海马nNOS表达 ;EGb有减轻神经元损伤 ,保护神经元的作用 ,其与Venlafaxine合用可能会达到对抑郁进行多靶点、多层次的治疗 ,弥补单一用药的不足。     

An NMDA antagonist in the MPOA impairs copulation and stimulus sensitization in male rats

Systemic injections of an NMDA antagonist have been shown to impair mating in male rats. One site where glutamate and its NMDA receptors may contribute to mating is the medial preoptic area (MPOA), which is vital for male sexual behavior. Glutamate is released in the MPOA during copulation, and especially at the time of ejaculation. We report here that the NMDA antagonist MK-801, microinjected into the MPOA, impaired copulatory behavior in sexually na?ve as well as experienced males. In rats tested both as na?ve and after sexual experience, drug treatment produced more profound impairment in na?ve males. In addition, MK-801, microinjected into the MPOA before each of 7 noncopulatory exposures to receptive female rats, resulted in copulatory impairments on a drug-free test on Day 8, relative to aCSF-treated rats; their behavior was similar to that of males that had not been preexposed to females. Therefore, NMDA receptors in the MPOA contribute to the control of copulation and stimulus sensitization. Glutamate, acting via NMDA receptors, regulates many neural functions, including neuronal plasticity. This is the first demonstration that a similar mechanism in the MPOA sensitizes male rats to the stimuli from a receptive female, and thereby enhances their behavior.     

Protective effects of Ginkgo biloba (EGb 761) on testicular torsion/detorsion-induced ischemia-reperfusion injury in rats

The aim of this study was to investigate the protective effect of Ginkgo biloba (EGb 761) on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups: control, I/R and I/R treated with EGb 761; each group contains 8 animals. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion. EGb 761 (50 mg/kg, orally) was administrated only once, 40 min prior to detorsion. To date, no more histopathological changes on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury in rats by EGb 761 treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in I/R groups were compared to the control group. Furthermore, EGb 761 treated animals showed an improved histological appearance in I/R group. Our data indicate a significant reduction in the activity of TUNEL and endothelial nitric oxide synthase (eNOS) in testes tissue of I/R treated with EGb 761 therapy. Electron microscopy of the testes of rats demonstrated that EGb 761 pretreatment was particularly effective in preventing the mitochondrial degeneration, dilatation of SER and enlarged intercellular spaces in both Sertoli and spermatid cells in I/R treated animals. We believe that further preclinical research into the utility of EGb 761 may indicate its usefulness as a potential treatment on testes injury after I/R in rats.     

Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors

Previously, our laboratory has shown that androgen receptors in the medial preoptic area (MPOA) and ventromedial nucleus (VMN) are necessary for copulation in male rats. The present study examined whether these receptors are required for other sociosexual behaviors. In Experiment 1, different regions of the VMN were implanted with the antiandrogen hydroxyflutamide (OHF). We found that implants located in anterodorsal portions of the VMN were more effective at inhibiting the restoration of copulation than implants in the posteroventral VMN. In Experiment 2, a second set of male rats was pretested for copulation and other sociosexual behaviors and was castrated. Experimental animals then received Silastic capsules filled with testosterone (T) plus intracranial (IC) implants filled with OHF to selectively block androgen receptors in either the MPOA or VMN. We found that androgen receptor blockade in the MPOA inhibited the restoration of copulation but had no effect on other sociosexual behaviors. OHF directed at the VMN inhibited the restoration of copulation and 50-kHz vocalizations but had no effect on scent marking. Two tests were used to assay sexual motivation: partner preference and conditioned place preference (CPP). Both methods revealed impairments in sexual motivation in the VMN group but not in animals receiving OHF in the MPOA. Taken together, these data suggest that androgen receptors in the MPOA are essential for copulatory performance, while androgen receptors in the VMN are important for copulation, sexual motivation, and androgen-dependent vocalizations.     

银杏叶提取物对血管性痴呆大鼠海马突触素表达的影响

目的：研究银杏叶提取物(EGb761)对血管性痴呆模型大鼠海马突触素表达的影响。方法:以双侧颈总动脉反复夹闭再通同时腹腔注射硝普钠建立血管性痴呆模型大鼠，采用Morris 水迷宫和免疫组化方法分别观察大鼠空间学习记忆能力及海马突触素(SYN)表达情况。结果:模型组大鼠在1月、2月和4月不同时点测得的Morris水迷宫逃避潜伏期(EL)均较假手术组明显延长(P<0.01)，药物组EL均显著短于模型组，但仍长于假手术组(P<0.05或P<0.01)；模型组海马SYN表达弱于假手术组，而药物组海马SYN表达高于模型组(P<0.01)。结论:EGb761增加海马结构SYN表达可能是其改善VD大鼠学习记忆障碍的重要机制。     

Dopamine and serotonin: influences on male sexual behavior

Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.     

Dopamine, the medial preoptic area, and male sexual behavior

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.     

Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice

Diabetes mellitus (DM) is caused by either destruction of pancreatic β-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1β and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.     

Effects of long‐term inhibition of neuronal nitric oxide synthase on blood pressure and renin release

Nitric oxide (NO) produced by neuronal NO‐synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7‐Nitro indazole (7‐NI) inhibits nNOS, and we investigated the effect of short‐ (4 days) and long‐term (4 weeks) 7‐NI treatment on blood pressure (BP), plasma renin concentration (PRC) and glomerular filtration rate (GFR) in rats on different salt diets. Rats were divided into three groups and given low‐salt (LS), normal (C) and high‐salt (HS) diets. Each diet group was subdivided into two groups treated either with 7‐NI or vehicle. Long‐term 7‐NI‐treated rats (LS and C) showed increased BP compared with controls (LS: 149 ± 4 vs. 133 ± 3; C: 146 ± 4 vs. 127 ± 4 mmHg). Blood pressure in HS rats did not differ from that in controls. Plasma renin concentration was stimulated in LS‐rats (251 ± 64 mGU mL^–1) compared with C and HS rats (42 ± 8 and 39 ± 5 mGU mL^–1, respectively) but was not significantly affected by chronic 7‐NI treatment (350 ± 103, 49 ± 10 and 50 ± 15 mGU mL^–1 in LS, C and HS, respectively). In rats treated with 7‐NI for 4 days, no effect on BP was seen, but PRC was increased in 7‐NI treated LS rats compared with vehicle treated LS rats (107 ± 15 vs. 56 ± 1 mGU mL^–1). Stimulation of PRC in LS rats was further enhanced by 7‐NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure.     

Dopamine release in the medial preoptic area of female rats in response to hormonal manipulation and sexual activity

Dopamine (DA) is responsive to hormonal manipulations and has been implicated in the regulation of female rat sexual behavior. In the present studies, extracellular DA levels were assessed in the medial preoptic area (MPOA) of ovariectomized female rats in response to exogenous ovarian hormones and during sexual activity. In female rats primed with a low dose of estradiol benzoate (2 microg), but not with a higher dose (20 microg), a 500-microg progesterone injection increased extracellular DA and facilitated copulatory behavior. Extracellular DA levels in the MPOA were further augmented during sexual interactions with a male rat in a nonpacing copulatory chamber by either perineal or vaginal stimulation. However, in a pacing chamber, DA efflux did not increase, although the metabolites rose significantly during copulation. Together, these findings suggest that extracellular DA in the MPOA responds to the hormonal state of the female rat and may contribute to her expression of sexual behavior.     

慢性疲劳应激对大鼠伏隔核一氧化氮合酶表达的影响

目的:探讨长时间游泳引起的疲劳应激对大鼠伏隔核(NAc)中神经元型一氧化氮合酶(nNOS)表达的影响.方法:采用成年雄性大鼠连续4周每天强迫游泳至力竭,用免疫组织化学方法结合图像处理测定伏隔核中nNOS的表达.结果:长时间强迫游泳应激可使大鼠伏隔核巾nNOS免疫细胞化学反应阳性神经元的数量(106.7%)、面积(150.2%)和灰度值(11.3%)显著增加.结论:nNOS参与疲劳应激的形成,一氧化氮在伏隔核对应激调节中起重要作用.     

Sexual motivation is demasculinized, but not feminized, in prenatally stressed male rats

Sexual motivation and copulation in male rats are associated with dopamine release in the nucleus accumbens. Demasculinized copulatory behavior has been demonstrated in prenatally stressed adult male rats. We have previously reported that approximately 80% of prenatally stressed male rats do not exhibit copulation and that no significant changes in nucleus accumbens dopamine release are seen during exposure to estrous females. In the present study, we investigated whether prenatal stress affects sexual motivation in these animals as adults. Pregnant Wistar rats were subjected to immobilization stress for two hours daily from day 15-19 of gestation. The prenatally stressed male offspring at the age of 3 months were allowed contact with receptive female rats for a 30 min period per week for 10 weeks; then, between the age of 5 and 6 months, their sexual motivation and copulatory activity were measured. Sexual motivation was measured in terms of sexual partner preference. The number of visits and the duration of each visit to an estrous female (stimulus female) or to a sexually active male rat (stimulus male) were recorded. Compared with control males, prenatally stressed male rats showed a significantly lower number of visits and a shorter duration of each visit to stimulus females. Prenatally stressed males showed no preference for male or female stimulus rats in terms of the number of visits and the duration of each visit, whereas control rats showed a significantly higher number of visits and duration of visits to female stimulus rats than male stimulus rats. A significant decrease in copulatory activity was observed in the prenatally stressed male offspring compared with control male rats, with most of the prenatally stressed males failing to show copulation. In vivo microdialysis experiments were performed on the nucleus accumbens with concurrent observation of sexual behavior. The prenatally stressed rats that did not exhibit copulation showed no significant changes in nucleus accumbens dopamine release during exposure to a stimulus male behind a wire-mesh barrier and the amount of dopamine release remained at the basal levels during actual physical contact. These results, combined with those of our previous report, indicate that sexual motivation in prenatally stressed male rats is demasculinized, but not feminized.     

糖尿病大鼠下丘脑视上核nNOS免疫阳性神经元的变化

目的：观察糖尿病大鼠下丘脑视上核神经元型一氧化氮合酶(nNOS)免疫阳性神经元数量的变化。方法：用链脲佐菌素诱导建立糖尿病大鼠模型；免疫细胞化学染色显示nNOS免疫阳性神经元，并进行定量分析。结果：糖尿病视上核nNOS免疫阳性神经元着色深浅不一，着色较深的阳性神经元散在分布，神经元的形态多样，突起较少。对照组大鼠视上核nNOS免疫阳性神经元较稀疏，各时期无明显改变。糖尿病2w，nNOS免疫阳性神经元数量与对照组无显著差异；7w，nNOS阳性神经元较密集，明显多于对照组；12w，nNOS免疫阳性神经元数量略低于7w，但仍多于对照组。结论：糖尿病大鼠下丘脑视上核nNOS免疫阳性神经元数量明显增多。     

不同剂量氯喹对戊四氮慢性致痫大鼠脑内nNOS表达的影响

目的:观察不同剂量氯喹对戊四氮慢性致痫大鼠脑内神经型一氧化氮合酶(nitric oxide synthase,nNOS)表达的影响,探讨氯喹在癫痫发生发展过程中的作用。方法:健康雄性SD大鼠50只,随机分为对照组(10只)、戊四氮致痫组(10只);氯喹干预1组(10只);氯喹干预2组(10只);氯喹干预3组(10只)。观察大鼠行为学表现,应用免疫组织化学和Western Blot方法观察不同剂量氯喹对慢性致痫大鼠脑内nNOS表达的影响。结果:戊四氮致痫组nNOS明显增多,与对照组相比差异具有显著性(P<0.05);氯喹可抑制nNOS的表达,氯喹干预2、3组与对照相比差异无显著性(P>0.05)。结论:氯喹能够剂量依赖性的抑制nNOS的表达,提示氯喹可通过其对nNOS的抑制作用达到抗癫痫效应。