Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

Conditioned locomotion and place preference elicited by tactile cues paired exclusively with morphine in an open field

A novel version of the conditioned place preference (CPP) technique was used in an attempt to determine whether tactile stimuli previously associated with morphine elicit approach and sustained contact. Empirical support for this view has been equivocal, prompting some to question the validity of the CPP technique. In the present study, rats received, during conditioning, morphine (10 mg/kg, IP) paired exclusively with an open field floor made of four quadrants of one texture (CS+) and saline with another floor made of four quadrants of a different texture (CS–). On the test for CPP, rats were given saline and placed in an open field containing either 1, 2, or 4 quadrants of the CS+ (with 3, 2, 0 quadrants of the CS–, respectively). These animals showed high absolute CPP scores on the test, spending, on average, as much as 83% and 75% of their time on the CS+ when two and one CS+ quadrants, respectively, were present. Concurrent measures of activity indicated that animals were most active when all four quadrants were CS+ and least active when zero or one CS+ quadrant was present. Thus, once an animal approached and made contact with the CS+ it tended to maintain contact with this stimulus and to reduce its approach to and contact with other stimuli. The differentiating features of this version of the CPP technique, as well as the relationship between morphine-induced conditioned locomotion and CPP, are discussed.     

Repeated testing attenuates conditioned place preference with cocaine

Cocaine-treated rats acquired a preference for cocaine-associated contextual stimuli (CS) relative to saline-injected control rats. However, when animals were given repeated tests for conditioned place preference intermittent between conditioning trials, they displayed an attenuation in strength of conditioning. This attenuation was not due to pharmacologic tolerance (Experiment 1), but rather reflected a disruption in learning due to exposure to the CS alone (Experiment 2). Like other examples of classical conditioning, the strength of the conditioned response (CR) as assessed by the conditioned place preference model may be influenced by partial reinforcement.     

竹林区村庄白纹伊蚊孳生特点的调查

白纹伊蚊在竹林里孳生的阳性比为75.4%;而在竹林包围的居民区阳性比为15.3%。白纹伊蚊在居民区孳生密度布雷图指数为19.4,容器指数为6.2%。居民区孳生蚊虫的主要场所是泡菜坛,泡菜坛主要孳生蚊种是骚扰阿蚊,阳性比为73.7%,其次是淡色库蚊为20.2%,贪食库蚊为14.0%,白纹伊蚊最低,为9.1%。     

左旋四氢巴马汀对苯丙胺条件性位置偏爱效应的影响

目的　观察左旋四氢巴马汀 (l-tetrahydropalmatine ,l-THP)对苯丙胺 (Amphetamine,AA)的条件性位置偏爱 (conditionalplacepreference,CPP)效应的影响。方法　采用倾向性训练程序训练大鼠 ,建立位置偏爱模型和建立氢化可的松诱发位置偏爱效应重现模型 ,并观察l-THP对其影响。结果　l-THP 10mg·kg-1可阻断AA 2 .0mg·kg-1的位置偏爱效应 ,并且可阻止氢化可的松 10mg·kg-1诱发的位置偏爱效应的重现。结论　AA可使大鼠出现条件性位置偏爱效应 ,并在一定剂量范围内 (0 .5～ 4.0mg·kg-1)呈量效关系 (r=0 .94) ;氢化可的松可使已消失的位置偏爱效应重现 ;以上 2种效应均可被l-THP阻断。     

优良资源植物——三颗针的质量考查研究之二

对四种同季不同产地采集的“三颗针”不同部位的四种生物碱进行了含量测定和分析,为该类药材的质量研究、生药采收、药厂选投料及开发应用等提供了科学依据。同时对该类资源的可持续利用也具有积极意义。     

In vivo microdialysis and conditioned place preference studies in rats are consistent with abuse potential of tramadol.

The abuse potential of tramadol was investigated using both in vivo microdialysis measures of dopamine (DA) release within the nucleus accumbens (NAc) shell and the conditioned place preference (CPP) paradigm in rats. Tramadol (75 mg/kg, i.p.) induced a statistically significant increase (starting 80 min posttreatment) in DA release within the NAc shell, which was maintained for at least 120 min posttreatment. Tramadol (18.75, 37.5, and 75 mg/kg i.p.) produced a statistically significant CPP, with the effects of the two highest doses comparable to those induced by morphine (5 mg/kg, s.c.). The release of DA within the NAc shell may be responsible for the rewarding properties of tramadol and, together with the CPP results, provide evidence that tramadol may possess greater abuse potential than originally believed.     

攀枝花市公共场所基本卫生状况分析

本文攀枝花市公共场所环境卫生质量进行了调查和分析。结果表明：空气中细菌总数超标８２．７％，气湿超标７１％，风速超标５４．３％，噪声超标４５．６％，ＣＯ２超标１３．６％，ＣＯ超标９％。为改善公共场所卫生质量提出了建议。