不同一线化疗方案治疗老年晚期胃癌的近期临床疗效观察★

目的 比较不同一线化疗方案治疗老年晚期胃癌的近期疗效及不良反应。方法 选择2017年1月1日—2019年12月31日我院收治的111例老年晚期HER-2阴性胃癌患者为研究对象，所有患者均经病理组织学或细胞学确诊。其中65例患者采用SOX方案：奥沙利铂130 mg·m^-2静脉滴注，d1+替吉奥80 mg·m^-2·d^-1口服，bid，d1-d14，21 d为1个周期；46例患者采用TS方案：多西紫杉醇75 mg·m^-2静脉滴注，d1+替吉奥80 mg·m^-2·d^-1口服，bid ，d1-d14，21 d为1个周期。所有患者均连续治疗2个周期以上。评价并比较两组患者的近期疗效和不良反应。结果 SOX组客观有效率（ORR）为55.38%（36/65），疾病控制率（DCR）为84.62%（55/65）；TS组ORR为52.17%（24/46），DCR为89.13%（41/46）；TS组DCR略高于SOX组，但差异无统计学意义（P>0.05）。两组患者的不良反应主要为骨髓抑制和胃肠道反应，SOX组1～2级贫血的发生率高于TS组，差异有统计学意义（72.31% vs. 43.48 %， P=0.002）。SOX组和TS组的无进展生存期（PFS）分别为（6.9±2.9）个月、（8.2±3.7）个月，差异有统计学意义（P=0.040）；总生存期（OS）分别为（13.9±5.7）个月、（13.3±5.9）个月，差异无统计学意义（P>0.05）。结论 与SOX方案相比，TS方案一线治疗老年胃癌的近期疗效相似，不良反应发生率较低，患者PFS显著延长，在老年晚期胃癌的治疗中更具优势。     

间硝苯地平对DOCA-satl 高血压大鼠心肌膜碎片二氢吡啶结合位点的影响

用 DOCA-salt 高血压大鼠心肌肥厚模型，观察间硝苯地平（m-Nif）对肥厚心肌膜碎片二氢吡啶（DHP）结合位点的影响。结果显示：预防或治疗性给予m-Nif（20 mg·kg^-1·d^-1）12 或 9 周，血压降低，心室重和心肌线粒体钙含量减少，且肥厚心肌DHP结合位点密度显著降低（450±25, 462±36 fmol·mg^-1 vs 836±47 fmol·mg^-1 protein, P<0.001）。提示：m-Nif预防和逆转DOCA-salt 高血压大鼠心肌肥厚的作用可能与其减少肥厚心肌DHP 结合位点密度和血压降低有关。     

培美曲塞联合吉西他滨与吉西他滨单药治疗胰腺癌患者的临床对照研究

目的 对比观察培美曲塞联合吉西他滨化疗与吉西他滨单药治疗胰腺癌的临床疗效,进一步优化胰腺癌化疗方案.方法 将72例非手术治疗的胰腺癌患者随机分为两组:联合化疗组35例,静脉滴注培美曲塞600 mg/m²与吉西他滨1 000 mg/m²联合化疗.单药治疗组37例,吉西他滨单药600 mg/m²化疗,疗程均为4个周期(每个周期间隔21 d).26周进行近期疗效及安全性分析,随访2年观察患者生存期.结果 (1)疾病控制率(DCR):联合治疗组为62.86%,单药治疗组为51.35%,两组比较差异无统计学意义(χ²=0.97,P=0.32);但早期患者联合治疗组DCR(85.71%)优于单药治疗组(56.52%),两组比较差异有统计学意义(χ²=4.49,P=0.034);(2)生存时间:联合治疗组中位生存时间为8.9个月,单药治疗组为8.1个月,两组比较无统计学差异.(3)不良反应:联合治疗组粒细胞、血小板减少和肝功能异常的发生率(60.2%、53.9%、54.2%)均高于单药组(32.1%、24.3%、27.0%),差异有统计学意义(P <0.05).结论 培美曲塞与吉西他滨联合化疗可以提高早期胰腺癌患者的疗效,同时也相应地增加对骨髓造血功能的抑制和肝损伤的风险.     

小剂量地西他滨对骨髓增生异常综合征患者的疗效及对IL-13、IL-18和IL-32的影响

目的 探讨小剂量地西他滨对骨髓增生异常综合征（MDS）患者的疗效及白细胞介素-13（IL-13）、白细胞介素-18（IL-18）和白细胞介素-32（IL-32）水平的影响。方法 以2015年1月-2017年1月在新乡市第一人民医院接受诊治的60例MDS患者为研究对象。根据入院的时间先后顺序分为对照组和观察组各30例。两组患者均给予地西他滨,对照组用药剂量为25 mg/（m²·d）,观察组为10 mg/（m²·d）。比较两组治疗3个月后的疗效和不良反应发生情况以及治疗前后的IL-13、IL-18和IL-32水平。结果 两组的治疗总有效率分别为80.00%和76.67%,差异无统计学意义;两组的不良反应发生情况差异不具有统计学意义,但观察组的不良反应总发生率低于对照组。治疗前,两组的IL-13、IL-18和IL-32水平差异无统计学意义;两组治疗后的IL-13水平高于且IL-18和IL-32水平低于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）;治疗后,观察组的IL-13水平高于对照组,且IL-18和IL-32水平低于对照组,差异有统计学意义（P<0.05）。结论 地西他滨对MDS的疗效明显,剂量为10 mg/（m²·d）时临床效果好,不良反应少,可更有效改善免疫功能,并且更经济。     

膜性肾病患者他克莫司血浓度与给药剂量的相关性研究

摘 要 目的： 研究他克莫司治疗膜性肾病的有效血药浓度与给药剂量的相关性。 方法: 41例膜性肾病患者给予他克莫司联合小剂量激素治疗,采用均相酶扩大免疫分析法测定他克莫司全血谷浓度,根据患者24h尿蛋白、血浆白蛋白及肾功能变化进行临床疗效评价,分析他克莫司治疗膜性肾病的疗效与血药浓度及给药剂量的相关性。结果:完全缓解组患者他克莫司血药浓度为（7.47±2.74）ng·ml^-1,给药剂量为（0.047±0.007）mg·kg^-1·d^-1;部分缓解组血药浓度为（5.72±1.19）ng·ml^-1,给药剂量为（0.049±0.008）mg·kg^-1·d^-1;无缓解组血药浓度为（3.30±1.08）ng·ml^-1,给药剂量为（0.052±0.01）mg·kg^-1·d^-1。结论: 他克莫司血药浓度在（5.10～9.32）ng·ml^-1时有较好治疗效果,部分患者血药浓度不随给药剂量的增加而提高。     

环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病观察

摘 要 目的：探讨环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病的临床疗效和安全性。方法：进展性IgA肾病患者120例随机分为观察组和对照组每组60例。对照组晨起顿服大剂量泼尼松,起始剂量1.0 mg·kg^-1·d^-1,最大量60 mg·d^-1,6周后（或尿蛋白转阴后2周）逐渐减量,至12周时减至0.5 mg·kg^-1·d^-1,维持治疗;观察组给予环孢素A+泼尼松治疗,环孢素A起始剂量100 mg·d^-1,根据血药浓度调整用量,最大不超过5.0 mg·kg^-1·d^-1, 使环孢素 A 谷浓度维持在100～200 mg·ml^-1;波尼松起始剂量0.5 mg·kg^-1·d^-1,最大量30 mg·d^-1。两组均治疗6个月以上。分别于治疗2,4,6,8,12,24周观察两组患者24 h 尿蛋白、血白蛋白、肌酐、尿酸等指标变化,评价两组的临床疗效和药品不良反应。结果：观察组治疗4,8,12,24周时的总缓解率均显著高于对照组（P<0.05）。治疗2,4,8,12,24周时,两组24 h 尿蛋白均显著下降（P<0.05）,且观察组明显低于对照组（P<0.05）。观察组治疗4,8,12,24周时血白蛋白较治疗前显著上升（P<0.05）,且显著高于对照组同期（P<0.05）;而对照组治疗期间血白蛋白无明显变化（P>0.05）。治疗前后两组患者血肌酐和尿酸水平比较,差异无统计学意义（P>0.05）。两组药品不良反应发生率比较,差异无统计学意义（P>0.05）。结论：环孢素A联合中/低剂量泼尼松治疗进展性IgA肾病临床疗效好,安全性高,值得临床推广。     

UPLC法同时测定市售菟丝子中5种化学成分的含量

目的 采用UPLC法同时测定市售菟丝子中5种化学成分的含量。方法 采用Agilent SB-C₁₈（100 mm×2.1 mm,1.8 μm）;流动相为乙腈-0.2%甲酸水溶液进行梯度洗脱;流速：0.4 mL·min^-1;柱温：35℃;分段检测波长：1~5 min,325 nm;5~12 min,260 nm;12~30 min,360 nm。结果 5种成分的检测范围分别为绿原酸：0.50~200.09 mg·L^-1（r =0.999 9）、金丝桃苷：0.56~226.32 mg·L^-1（r =0.999 9）、异槲皮苷：0.45~180.60 mg·L^-1（r =0.999 9）、紫云英苷：0.43~173.07 mg·L^-1（r =0.999 9）、山柰酚：0.43~173.28 mg·L^-1（r =0.999 9）;平均回收率（n = 9）分别为 102.0%（RSD=1.56%）,99.0%（RSD=2.90%）,100.1%（RSD=3.19%）,100.2%（RSD=3.00%）,99.3%（RSD=4.25%）。结论 该方法简便、可靠,可用于菟丝子的质量评价,为进一步提高和完善菟丝子质量标准提供参考。     

兰索拉唑药物不良反应的Meta分析

目的 系统评价兰索拉唑临床应用中的药物不良反应（ADR）。方法 计算机检索 PubMed、Embase、CochraneLibrary、中国学术期刊全文数据库（CNKI）、万方数据库（Wanfang Data）和中国生物医学文献数据库（CBM），检索时限均为建库起至 2022年 9月 1日，收集兰索拉唑在临床应用中 ADR的随机对照试验（RCT），采用 RevMan 5.4统计软件进行Meta分析。结果 共纳入23项 RCTs，共计10 980 例患者。Meta分析结果显示，在ADR 总体发生情况［OR＝0.79，95%CI（0.69，0.90），P＝0.000 4］和胃肠道系统损害［OR＝0.44，95%CI（0.32，0.62），P＜0.000 01］中，试验组ADR发生率低于对照组，差异有统计学意义。在中枢及外周神经系统损害［OR＝0.80，95%CI（0.54，1.18），P＝0.27］、呼吸系统损害［OR＝1.67，95%CI（0.67，4.15），P＝0.27］、皮肤及其附件损害［OR＝1.24，95%CI（0.33，4.69），P＝0.75］中，试验组ADR发生率与对照组的差异无统计学意义。15 mg·d^-1亚组的ADR发生率低于对照组［OR＝0.66，95%CI（0.44，0.99），P＝0.04］，30 mg·d^-1 亚组［OR=0.89，95%CI（0.76，1.05），P＝0.16］和60 mg·d^-1 亚组 ［OR=0.76，95%CI（0.37，1.56），P＝0.46］的 ADR 发生率与对照组差异无统计学意义；疗程≤30 d亚组［OR＝0.60，95%CI（0.46，0.77），P＜0.000 1］ADR发生率低于对照组，疗程＞30 d亚组［OR＝0.87，95%CI（0.75，1.01），P＝0.07］ADR发生率与对照组差异无统计学意义；消化性溃疡亚组［OR＝0.71，95%CI（0.56，0.92），P＝0.008］ADR发生率低于对照组，胃食管返流病亚组［OR＝0.93，95%CI（0.78，1.10），P＝0.39］ADR发生率与对照组差异无统计学意义。结论 兰索拉唑安全性良好，患者的给药剂量为30 mg·d^-1和60 mg·d^-1、疗程＞30 d、临床诊断为胃食管返流病，其ADR发生率明显增加。     

右美托咪定复合舒芬太尼对结肠癌根治术后镇痛及免疫功能与应激反应的影响

目的 探究右美托咪定复合舒芬太尼对结肠癌根治术后镇痛及免疫功能与应激反应的影响。方法 选择2016年7月—2018年7月我院收治的行结肠癌根治术的患者96例为研究对象,按照随机数表法分成对照组（n=48）和观察组（n=48）。两组患者手术麻醉方式相同,术后镇痛对照组采用1.0 μg·kg^-1·d^-1舒芬太尼+8.0 mg托烷司琼;观察组采用1.5 μg·kg^-1·d^-1右美托咪定+1.0 μg·kg^-1·h^-1舒芬太尼+8.0 mg托烷司琼;两组患者均采用自控镇痛。分别评价两组患者术后0 h（T1）、4 h（T2）、8 h（T3）、24 h（T4）的镇痛效果（VAS及Ramsay评分）、免疫功能水平（IgG、IgA、IgM、CD4⁺及CD8⁺ T细胞）、应激水平［促肾上腺皮质激素（ACTH）、皮质醇（Cor）、醛固酮（ALD）］、血清S-100β及神经元特异性烯醇化酶（NSE）水平、不良反应的发生情况。结果 两组患者镇痛效果存在明显差异,同时间点观察组VAS评分明显低于对照组（P<0.05）,Ramsay评分明显高于对照组（P<0.05）;免疫功能与应激反应方面,T4时间点观察组患者免疫功能指标IgG、IgA、IgM、CD4⁺ T细胞水平均明显高于对照组（P<0.05）,CD8⁺ T细胞水平显著低于对照组（P<0.05）,应激指标ACTH、Cor及ALD水平均明显低于对照组（P<0.05）;T1时间点两组患者血清S-100β、NSE水平均无明显差异（P>0.05）,T4时间点观察组血清S-100β、NSE水平均明显低于对照组（P<0.05）;药物安全性方面,观察组恶心呕吐的发生率明显低于对照组（6.25% vs. 20.83%, P<0.05）,心动过缓的发生率明显高于对照组（20.83% vs. 6.25%, P<0.05）。结论 右美托咪定复合舒芬太尼对结肠癌患者的术后镇痛效果好,可增强免疫功能,减轻应激反应,降低血清S-100β、NSE水平。     

UPLC-MS/MS测定大鼠血浆中香附烯酮和α-香附酮浓度及其药动学研究

目的 建立UPLC-MS/MS测定大鼠血浆中香附烯酮和α-香附酮的方法，并研究其药动学。方法 采用Phenomennex C₁₈(150 mm×2.0 mm，3 μm)色谱柱，以乙腈-水为流动相进行梯度洗脱，柱温30 ℃，进样量1 μL，蛇床子素为内标，采用电喷雾离子源，正离子模式，香附烯酮m/z为219.1/135.1，α-香附酮m/z为219.1/111.0，蛇床子素m/z为245.0/123.0。检测大鼠血浆中香附烯酮、α-香附酮的浓度，应用DAS 2.0软件拟合主要的药动学参数。结果 香附烯酮在10~500 ng·mL^-1内线性关系良好(r=0.991 0)，α-香附酮在2.5~300 ng·mL^-1内线性关系良好(r=0.994 1)，日内精密度RSD＜9.45%，日间精密度RSD＜9.09%，加样回收率＞86.79%。SD大鼠灌胃给予香附挥发油提取物(20 mg·kg^-1)后，香附烯酮和α-香附酮C_max、AUC_0-∞、MRT_(0-∞)分别为(8 862.59±1 106.81)ng·L^-1，(7 060.94±774.25)ng·L^-1·h，(3.21±0.72)h和(934.69±106.81)ng·L^-1，(792.26±74.52)ng·L^-1·h，(4.94±0.82)h。结论 建立的方法能够快速、准确测定血浆中香附烯酮和α-香附酮的浓度，可用于香附烯酮和α-香附酮在大鼠体内的药动学研究。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.