SNP抑制5-HT诱导的胞内游离钙浓度升高和内钙释放

用Ｆｕｒａ － ２／ＡＭ 荧光测量技术研究了５ － 羟色胺（５－ ＨＴ） 诱导的大鼠尾动脉平滑肌细胞胞内钙升高和一氧化氮（ＮＯ） 的抑制效应。实验表明, 胞外０ｍ ｍｏｌ／ Ｌ Ｃａ２ ＋ 时胞内静息［Ｃａ２ ＋ ］ ｉ 为２０ ．２±８ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ８） 。１０μｍｏｌ／Ｌ ５－ ＨＴ 可诱导出胞内钙库释放引起的瞬态［Ｃａ２ ＋］ｉ 升高,其峰值达２４５ ．７ ±７１．６ｎｍｏｌ／ Ｌ（ｎ ＝ ６） 。１０ － ７ ｍｏｌ／Ｌ 硝普钠（ＳＮＰ） 可抑制５－ ＨＴ 诱导的［Ｃａ２ ＋］ｉ 升高,其峰值浓度降为７５．１±３５ ．９ｎｍｏｌ／Ｌ（ｎ ＝ ５） 。当细胞浴液含２．５ｍ ｍｏｌ／Ｌ Ｃａ２ ＋ 时,静息［Ｃａ２ ＋］ｉ为１１２ ．８ ±１０ ．３ｎｍｏｌ／ Ｌ（ｎ ＝ ５） , 这时１０μｍｏｌ／ Ｌ ５ － ＨＴ 可诱导［Ｃａ２ ＋ ］ ｉ 的峰值为２５２ ．３ ±８０ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ４） ,以及其后平台浓度为１４３ ．０ ±３７ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ４） ,略大于［Ｃａ２ ＋］ｉ 为１１２．８ ±１０ ．３ｎｍｏｌ／Ｌ 的静息浓度,为外钙内流引起。１０ － ７ ｍｏｌ／Ｌ ＳＮＰ 也可抑制５－ ＨＴ 诱导［Ｃａ２ ＋ ］ｉ 平台相浓度。平台浓度由１４３ ±４７     

5—HT对大鼠新鲜分离DRG神经元GABA激活电流的调制作用

本实验在新鲜分离的大鼠背根神经节（ＤＲＧ）细胞上应用全细胞膜片钳技术,观察５－ＨＴ对ＧＡＢＡ激活电流的调制作用。结果发现,绝大多数细胞（４９／５４）对ＧＡＢＡ（１０－８～１０－３ｍｏｌ／Ｌ）产生浓度依赖性的内向电流,并有明显的去敏感现象。在多数细胞预加５－ＨＴ（１０－７～１０－４ｍｏｌ／Ｌ）,ＧＡＢＡ激活电流受到明显抑制,抑制率分别为３．０％,１３．５％,１９．７％,２４．７％,５９．１％。５－ＨＴ（１０－７～１０－４ｍｏｌ／Ｌ）本身在部分细胞（２４／４０）可引起浓度依赖性的内向电流,部分细胞（１２／４０）未检测到膜电流,少数细胞（４／４０）可引起微弱的外向电流。此结果提示５－ＨＴ可能作用于初级传入终末,抑制ＧＡＢＡ引起的初级传入去极化从而调节ＧＡＢＡ的突触前抑制效应     

微电泳GABA和5－HT对大鼠丘脑束旁核单位痛放电的影响

本实验用多管微电极细胞外记录和离子微电泳方法,在水含氯醛麻醉的ＳＤ大鼠上观察了γ－氨基丁酸（ＧＡＢＡ）和５－羟色胺（５－ＨＴ）以及它们的受体阻断剂（印防已毒素和赛庚啶）对丘脑束旁核（Ｐｆ）单位痛放电的影响。结果表明：（１）电泳ＧＡＢＡ可抑制Ｐｆ神经元的痛放电,这作用可被电泳印防已毒素所阻断,而单独电泳印防己毒素可加强Ｐｆ的痛放电。（２）电泳５－ＨＴ对Ｐｆ单位痛放电在有些单位表现加强作用,另一些单位表现抑制作用,仅前者可被电泳赛庚啶所阻断。上述结果提示：在Ｐｆ神经元的痛放电活动中,ＧＡＢＡ可能起抑制性作用,而５－ＨＴ可能通过不同的受体亚型既发挥其兴奋作用,也可有抑制作用。     

乙酰胆碱对大鼠体外抗体生成的影响

目的：观察不同浓度乙酰胆碱（ＡＣｈ,１０－１０～１０－５ｍｏｌ／Ｌ）对大鼠体外抗体生成的影响,并初步探讨其作用机制,从细胞水平了解乙酰胆碱与免疫功能之间的关系。方法：用体外抗体生成的检测方法,用绵羊红细胞（ＳＲＢＣ）刺激大鼠肠系膜淋巴结Ｂ细胞转化成抗体形成细胞（ＡＦＣ）,然后检测其抗体生成量。结果：①１０－１０～１０－７ｍｏｌ／ＬＡＣｈ能显著抑制体外抗体生成,其中１０－８和１０－７ｍｏｌ／ＬＡＣｈ的作用较强,而１０－６和１０－５ｍｏｌ／ＬＡＣｈ无明显的抑制作用;②Ｍ型胆碱能受体激动剂毛果芸香碱（１０－８和１０－７ｍｏｌ／Ｌ）能明显减弱体外抗体生成,而Ｎ型受体激动剂烟碱（１０－８和１０－７ｍｏｌ／Ｌ）没有显著的减弱作用,Ｍ型受体拮抗剂阿托品（１０－７和１０－６ｍｏｌ／Ｌ）可完全阻断ＡＣｈ抑制体外抗体生成的作用;③ＡＣｈ分别在Ｂ细胞用ＳＲＢＣ刺激后３～４８ｈ中的６个不同时间与淋巴细胞作用,其抗体生成仍然是减少的。结论：ＡＣｈ可非浓度依赖性地抑制大鼠的体外抗体生成;此作用可能由Ｂ细胞上的Ｍ型胆碱能受体介导;且ＡＣｈ可能主要影响Ｂ细胞转化的后期过程。     

可乐定对背根神经节神经元GABA激活电流的抑制作用

本实验在新鲜分离大鼠背根神经节（ＤＲＧ）细胞上应用全细胞膜片的箝记录研究贤上腺素α２－受体激动剂可乐定（ｃｌｏｎｉｄｉｎｅ）对ＧＡＢＡ－激活电流的调制作用。发现缘大多数ＤＲＧ细胞对ＧＡＢＡ（１０＾－６￣１０＾－３ｍｏｌ／Ｌ）敏感（７２／７５）,产生浓度依赖性的内向电流;并且可被ｂｉｃｕｃｕｌｉｎｅ（１０＾－５￣１０＾－４ｍｏｌ／Ｌ）所阻断。在多数细胞中（５１／７２）预加可乐定（１０＾－８￣１０＾－     

中缝隐核投射至中脑导水管周围灰质腹侧部的递质分析

实验在戊巴比妥钠麻醉大鼠上进行。双侧中脑导水管周围灰质腹侧部（ｖＰＡＧ）微量注射１μｇ／μｌ肾上腺素（每侧０．１μｌ）,刺激中缝隐核（ＮＲＯ）引起的降压反应明显增强,但该效应可被ｖＰＡＧ预先注射心得安所阻断,而注射酚妥拉明对上述效应无明显影响;ｖＰＡＧ内单独微量注射１μｇ／μｌ心得安（每侧０．１μｌ）,可部分阻断ＮＲＯ降压反应,而注射１μｇ／μｌ酚妥拉明（每侧０．１μｌ）无明显影响;双侧ｖＰＡＧ微量注射１０μｇ／μｌ吗啡或０．１ｍｏｌ／Ｌ５－ＨＴ（每侧０．１μｌ）,基础血压无明显变化,ＮＫＯ的降压反应幅度减小（Ｐ＜０．０５）。提示,ＮＫＯ对ｖＰＡＧ的兴奋作用的可能递质为肾上腺素,通过β受体介导;吗啡或５－ＨＴ则可减弱ＮＲＯ对ｖＰＡＧ的兴奋性投射作用。     

皮质酮快速抑制PC12细胞乙酰胆碱诱发电流影响及机制探讨

目的和方法：本研究采用全细胞膜片箝技术,观察皮质酮（Ｂ）对ＰＣ１２细胞上乙酰胆碱诱发电流（ＩＡＣｈ）的快速作用并初步探讨其可能机制。结果：ＰＣ１２细胞上ＩＡＣｈ是通过烟碱受体（ｎＡＣｈＲ）引起的。箝制电压为－８０ｍＶ时,ＡＣｈ（３０μｍｏｌ／Ｌ）诱发一内向电流;细胞外灌流同时给予ＡＣｈ和Ｂ（１０－５ｍｏｌ／Ｌ）时,Ｂ对ＩＡＣｈ的抑制作用较弱;用Ｂ（１０－５ｍｏｌ／Ｌ）对细胞进行预处理,可提高Ｂ对ＩＡＣｈ峰值的抑制率,作用呈可逆性、浓度依赖性和非电压依赖性;细胞外用ＲＮＡ合成抑制剂放线菌素Ｄ（４×１０－５～４×１０－３ｍｏｌ／Ｌ）或蛋白合成抑制剂放线菌酮（１０－４～１０－３ｍｏｌ／Ｌ）孵育细胞１～２ｈ阻断基因机制,但均不影响Ｂ对ＩＡＣｈ的快速抑制作用。结论：Ｂ对ＰＣ１２细胞上ＩＡＣｈ有快速抑制作用,此作用可能是由非基因组机制介导的。     

组胺H_2受体激动剂和拮抗剂对WEHI_3细胞增殖的作用

近年来研究表明组胺及其受体在正常造血调控中起着重要作用。本研究用琼脂半固体培养技术观察了特异性组胺Ｈ２受体激动剂英普咪定和拮抗剂西咪替丁对髓系粒－单核细胞白血病干细胞株ＷＥＨＩ３细胞生长的影响。结果表明不同浓度的英普咪定（１０－８─１０－４ｍｏｌ／Ｌ）对集落数呈明显剂量依赖性抑制,与对照组比较ｐ＜０．０１。１０－１０─１０－９ｍｏｌ／Ｌ英普咪定对集落数无明显影响。１０－４─６×１０－４ｍｏｌ／Ｌ的英普咪定对集落产率的抑制作用趋于饱和。最大抑制效能为对照组的５４％（ｐ＜０．０１）。１０－４ｍｏｌ／Ｌ西咪替丁能完全阻断１０－８ｍｏｌ／Ｌ英普咪定的集落抑制作用。对≥１０－６ｍｏｌ／Ｌ英普咪定的作用西咪替丁均有部分阻断作用,与对照组比较Ｐ＜０．０１。单用西咪替丁对ＷＥＨＩ３细胞无明显直接作用。这提示ＷＥＨＩ３细胞株上存在有组胺Ｈ２受体,激动Ｈ２受体可抑制细胞增殖。     

钙通道阻滞剂对肾上腺素能受体激动剂促血管平滑肌细胞增值的抑制

本工作观察到１０－６—１０－５ｍｏｌ／Ｌ去甲肾上腺素（ＮＥ）和１０－７—１０－５ｍｏｌ／Ｌ异丙基肾上腺素（ＩＳＯ）可明显促进离体培养的血管平滑肌细胞（ＶＳＭＣ）的增殖和ＤＮＡ的合成,并呈剂量依赖效应,该效应可为相应的受体阻断剂ｐｈｅｎｔｏｌａｍｉｎｅ（１０－６ｍｏｌ／Ｌ）和ｐｒｏｐｔａｎｏｌｏｌ（１０－５ｍｏｌ／Ｌ）所抑制;ｎｉｆｅｄｉｐｉｎｅ（１０－６ｍｏｌ／Ｌ）和ｖｅｒａｒｏｍｉｌ（１０－６ｍｏｌ／Ｌ）分别与同样浓度的ＮＥ同时加入细胞培养液中,其细胞计数和３Ｈ－ＴｄＲ掺入率分别较单用ＮＥ时显著降低（Ｐ＜０．０１）,ｎｉｆｅｄｉｐｉｎｅ与ｖｅｒａｐａｍｉｌ亦明显抑制ＩＳＯ促ＶＳＭＣ增殖的作用。     

糖皮质激素及其他甾体激素对大鼠下丘脑薄片释放精氨酸加压素的影响

本工作采用离体孵育技术,观察大鼠下丘脑薄片（含有室旁核和视上核）释放精氨酸加压素（ＡＶＰ）和糖皮质激素（ＧＣ）及其他甾体激素对ＡＶＰ释放的快速影响。结果如下：（１）大鼠下丘脑薄片经过９０ｍｉｎ的恢复之后,在长达６ｈ的孵育过程中能够相当稳定地释放ＡＶＰ,释放量为９．０６±１．２３ｐｇ／ｍｉｎ;（２）皮质酮（Ｂ）在２０ｍｉｎ内可明显地抑制ＡＶＰ的释放,在１０－７—１０－４ｍｏｌ／Ｌ范围内呈剂量－效应关系;（３）在同一剂量（１０－６ｍｏｌ／Ｌ）,皮质醇、１７β－雌二醇和睾丸酮也可快速地抑制ＡＶＰ的释放,而相同剂量的地塞米松、醛固酮、孕酮、ＲＵ４８６和胆固醇却无此效应;（４）ＲＵ４８６（１０－７—１０－３ｍｏｌ／Ｌ）对ＡＶＰ的释放没有影响,但却能（１０－５—１０－３ｍｏｌ／Ｌ）部分地阻断Ｂ的快速抑制效应。这些结果表明,ＧＣ对大鼠下丘脑ＡＶＰ的释放具有不通过传统的基因组机制的快速抑制效应,此种抑制效应可能与ＧＣ的负反馈调节作用有关。     

Microelectrophoretic application of antagonists of putative neurotransmitters onto various types of bulbar respiratory neurons.

Seven antagonists of putative neurotransmitters were applied to bulbar respiratory neurons and, for comparison, also to unspecific cells. The antagonists exerted distinct effects when released alone, permitting to draw conclusions about receptor properties of the various cell types. With strychnine, specific antagonist of glycine, excitation prevailed in EI, I and E neurons. With bicuculline, specific antagonist of GABA, excitation preponderated in EI and E cells. About half of the unspecific neurons were activated and the remainder were unresponsive. GDEE (glutamatediethylester), antagonist of glutamate, excited part of the IE neurons and inhibited part of the E units, while the remainder of both types as well as 2 EI cells tested were not affected. With flupentixol, antagonist of dopamine, excitation prevailed in I neurons. About half of the IE and E units remained unaffected, while in the remainder E cells inhibition preponderated over excitation. With yohimbine, an alpha-adrenoceptor blocker, inhibition prevailed in E units. The two EI as well as the majority of the I neurons remained unaffected, with two cells of the latter type being activated. Propranolol, a beta-adrenoceptor blocker, inhibited about half of the E neurons, while the remainder as well as most IE and the 2 EI cells tested were not affected. Cyproheptadine, an antagonist of 5-HT, excited most E neurons. As concerns NE-receptors, those of the alpha-type might be involved in activation of part of the E cells only, whereas all other NE effects (inhibition or activation) are mediated by CNS-specific receptors different from the alpha- and beta-type. 5-HT effects apparently are mediated by two different receptor types.     

5-HT对弓状核神经元的直接兴奋作用和通过GABA能局部神经元实现的抑制作用

用大鼠离体灌流脑片的细胞外单一神经元电生理记录技术,观察了5－HT对弓状核神经元自发放电的影响。结果表明：（1）在随机选取的149个神经元中,有33个（22．2％）可被5－HT兴奋,82个（55．0％）被抑制,其余34个（22．8％）出现双相反应或不出现反应;（2）用低Ca^2 -高Mg^2 人工脑脊液替换正常人工脑脊液后,5－HT引起的兴奋效应仍可出现,但5－HT引起的抑制效应不再出现;（3）5－HT受体的非选择性拮抗剂cyproheptadine对5－HT引起的兴奋或抑制都有阻断作用;（4）用GABA受体拮抗剂bicuculline(Bic)可以阻断5－HT引起的抑制作用。据此推测：（1）5－HT的兴奋效应对低Ca^2 环境不敏感,因而是5－HT直接作用于所记录细胞的结果;（2）5－HT的抑制效应对低C a^2 敏感,并可被Bic所阻断,因而－HT可能是兴奋了局部GABA能中间神经元,后者再通过释放GABA抑制了所记录的神经元。     

皮质酮对大鼠下丘脑薄片室旁核神经元自发电活动的影响

本实验应用离体大鼠下丘脑薄片技术,用玻璃微电极细胞外记录、观察了下丘脑室旁核神经元的自发电活动,以及皮质酮对自发电活动的影响。在36个下丘脑薄片上观察了104个室旁核神经元的自发电活动,其放电形式主要有三种:慢而不规则(50个,占48.1%)、快速连续(44个,占42.5%)和周期性放电(10个,9.4%)。在进行皮质酮灌流的实验中,这104个单位有25个在皮质酮(10~(-7),10~(-6)mol/L)作用后,自发放电明显减少,有8个单位出现兴奋效应;其余的没有观察到明显反应。上述33个产生反应的神经元其反应特点是:潜伏期短、反应的程度与皮质酮浓度有关、糖皮质激素胞液受体阻断剂 RU38486可以阻断这种反应。结果表明糖皮质激素可以快速影响下丘脑薄片内某些室旁核神经元的电活动,为甾体激素的快速非基因机制作用提供了新的证据,提示室旁核神经元膜上有糖皮质激素受体存在。     

An analysis of the 5-hydroxytryptamine (serotonin) receptor subtypes of central neurones of Helix aspersa.

1. Intracellular recordings were made from identified neurones in the central nervous system of Helix aspersa. Two types of cell were used, those excited by 5-hydroxytryptamine (5-HT) and acetylcholine and those inhibited by 5-HT and dopamine. The actions of a range of 5-HT agonists and antagonists were tested for their ability to interact with 5-HT receptors. 2. 5-Carboxyamidotryptamine, alpha-methyl-5-HT and N-methyl-5-HT were active on cells excited by 5-HT, with similar potencies to 5-HT. Only 5-carboxyamidotryptamine and 5-methoxytryptamine were equiactive with 5-HT on cells inhibited by 5-HT. Most of the non-indole analogues were inactive or very weak agonists on both receptors. 3. MDL 72222 was the most active antagonist tested against 5-HT excitation, showing some selectivity for 5-HT over acetylcholine. Cinanserin and ketanserin also showed selectivity for 5-HT over acetylcholine. 4. Tryptamine was inhibitory on both cell types and was a potent antagonist of 5-HT excitation, showing selectivity for 5-HT over acetylcholine. 5. It is concluded that the 5-HT excitatory receptor recognizes the indole nucleus with substitution on position 5, save for 5-fluorotryptamine which was inhibitory. It does not appear that these 5-HT receptors can be classified in terms of the vertebrate subtypes of 5-HT receptor. However, it should be noted that only two receptor subtypes located on a small number of neurones were studied in these experiments and other 5-HT receptor suptypes may be located on other groups of neurones and peripheral tissues. These receptors may recognize other 5-HT receptor ligands including non-indoles.     

微电泳给予单胺类受体阻断剂对兔孤束区呼吸性单位的吗啡诱发抑制效应的影响

实验在46只局部麻醉、肌肉麻痹和切断双侧颈迷走神经的家兔上进行。记录延髓孤束区的单位放电活动。观察微电泳单胺类受体阻断剂对呼吸性单位的吗啡诱发抑制效应的影响。全身应用吗啡前,在86个吸气性单位中,妥拉苏林引起阻遏的只有9个,在92个吸气性单位中,赛庚啶引起兴奋的只有1个。而在全身应用吗啡诱发单位活动抑制的背景上,在59个吸气性单位中,妥拉苏林引起阻遏的有42个,在74个吸气性单位中,赛庚啶引起兴奋的有12个。但两者对非呼吸性单位的影响,吗啡应用前后均无明显差别。这些结果进一步支持下述假设,即在吗啡所致的呼吸抑制效应中,5-HT 可能起着抑制性递质的作用,而 NE 起着兴奋性递质的作用。     

An analysis of the 5-hydroxytryptamine (serotonin) receptor subtypes of central neurones of Helix aspersa

1. Intracellular recordings were made from identified neurones in the central nervous system of Helix aspersa. Two types of cell were used, those excited by 5-hydroxytryptamine (5-HT) and acetylcholine and those inhibited by 5-HT and dopamine. The actions of a range of 5-HT agonists and antagonists were tested for their ability to interact with 5-HT receptors.2. 5-Carboxyamidotryptamine, α-methyl-5-HT and N-methyl-5-HT were active on cells excited by 5-HT, with similar potencies to 5-HT. Only 5-carboxyamidotryptamine and 5-methoxytryptamine were equiactive with 5-HT on cells inhibited by 5-HT. Most of the non-indole analogues were inactive or very weak agonists on both receptors.3. MDL 72222 was the most active antagonist tested against 5-HT excitation, showing some selectivity for 5-HT over acetylcholine. Cinanserin and ketanserin also showed selectivity for 5-HT over acetylcholine.4. Tryptamine was inhibitory on both cell types and was a potent antagonist of 5-HT excitation, showing selectivity for 5-HT over acetylcholine.5. It is concluded that the 5-HT excitatory receptor recognizes the indole nucleus with substitution on position 5, save for 5-fluorotryptamine which was inhibitory. It does not appear that these 5-HT receptors can be classified in terms of the vertebrate subtypes of 5-HT receptor. However, it should be noted that only two receptor subtypes located on a small number of neurones were studied in these experiments and other 5-HT receptor subtypes may be located on other groups of neurones and peripheral tissues. These receptors may recognize other 5-HT receptor ligands including non-indoles.     

Potent inhibitory effect of selective D2 and D3 agonists on dopamine-responsive dorsomedial arcuate neurons in brain slices of estrogen-primed rats.

The possible involvement of dopamine D2 and D3 receptors in the action of dopamine (DA) on inhibiting dorsomedial arcuate nucleus (dmARN) neurons in brain slices was determined in this study. Fresh brain slices were prepared from ovariectomized, estrogen-primed Sprague-Dawley rats and used for extracellular single-unit recording. The dmARN neurons were first identified by their inhibitory responses to DA and then tested with PHNO and/or PD128907, selective D2 and D3 agonists, respectively. PD128907 in 5-50 nmole doses significantly inhibited the majority of DA-responsive dmARN neurons (86.3% of 44 units). Moreover, PHNO in 5-25 nmole doses inhibited all DA-responsive neurons tested (100% of 34 units). The inhibitory effects of PHNO and PD128907 were not only prominent; but also persisted in low Ca2+, high Mg2+ medium, indicating that they were acting directly on the recorded neuron. Pretreatment of either raclopride or U99194A, D2 and D3 receptor antagonists respectively, reversed the effects of DA in a few trials. In contrast, SKF81297, a D1 receptor agonist, induced variable responses in dmARN neurons. These results clearly indicate that DA may act through D2 and/or D3 receptors to exhibit an inhibitory effect on presumed TIDA neurons in dmARN.     

Staphylococcal enterotoxin induces emesis through increasing serotonin release in intestine and it is downregulated by cannabinoid receptor 1

Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are the most recognizable bacterial superantigenic toxins causing food poisoning in humans throughout the world. However, it remains unclear how SEs induce emesis and its emetic signal pathway. We investigated a mechanism of SEA-induced emesis using a small emetic animal model, house musk shrew. SEA-induced emesis in the animals was inhibited by a 5-hydroxytryptamine (5-HT) synthesis inhibitor and a 5-HT(3) receptor antagonist. SEA could increase 5-HT release in the small intestine. Pre-treatment with 5,7-dihydroxytryptamine (5,7-DHT) markedly inhibited SEA-induced emesis. SEA-induced emesis was also abolished by surgical vagotomy. Furthermore, cannabinoid (CB) receptor agonists inhibited SEA-induced emesis, and the action was reversed by a CB1 antagonist. Both 5-HT release and CB1 receptor expression were found in the mucosal and myenteric plexus of the intestine. Moreover, a CB1 receptor agonist significantly decreased the 5-HT release in the intestine. These results demonstrate that SEA induces 5-HT release in intestine, rather than in brain, and that the 5-HT(3) receptors on vagal afferent neurons are essential for SEA-stimulated emesis. In addition, SEA-induced emesis is downregulated by the CB system through decreasing 5-HT release in intestine.     

Curcumin prevents corticosterone-induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway

Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT(1A), 5-HT(2A) and 5-HT(4), but 5-HT(1B,) 5-HT(2B), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors remain unchanged. Pre-treatment with curcumin reversed this effect on mRNA for the 5-HT(1A) and 5-HT(4) receptors, but not for the 5-HT(2A) receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone-induced neuronal death. This observed effect of curcumin was partially blocked by either 5-HT(1A) receptor antagonist p-MPPI or 5-HT(4) receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone-induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p-MPPI and RS 39604 reversed the effect of curcumin-induced change in neuronal morphology and synaptophysin expression of corticosterone-treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p-MPPI. However, curcumin-induced elevation in protein kinase A activity and phosphorylation of cAMP response element-binding protein levels were inhibited by both p-MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5-HT receptor-cAMP-PKA-CREB signal pathway.