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1.
Lesley A Ricci Daniel F Connor Randall Morrison Richard H Melloni 《Neuropsychopharmacology》2007,62(3):218-225
BACKGROUND: Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27-57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. METHODS: Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05-1.0 mg/kg, intraperitoneally). RESULTS: Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1-.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3-1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. CONCLUSIONS: These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression. 相似文献
2.
BACKGROUND: Aripiprazole (Abilify) is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D2 receptors and low side effects. Based on pharmacologic properties that include a stabilization of mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole was tested for its ability to prevent relapse to cocaine seeking in rats. METHODS: We assessed the dose-dependent effects of aripiprazole on conditioned cue-induced and cocaine-primed reinstatement of drug-seeking behavior following chronic intravenous cocaine self-administration in an animal model of relapse. RESULTS: Aripiprazole potently and dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned-cued reinstatement. Aripiprazole was effective at doses that failed to alter cocaine self-administration, food self-administration, reinstatement of food-seeking behavior, or basal locomotor activity, suggesting selective effects of aripiprazole on motivated drug-seeking behavior. CONCLUSIONS: These results in a relapse model show that aripiprazole can block cocaine seeking without affecting other behaviors. The D2 partial agonist properties of aripiprazole likely account for the blockade of reinstatement of cocaine-seeking behavior. Given its established efficacy and tolerability as a treatment for psychosis, aripiprazole may be an excellent therapeutic choice for reducing craving and preventing relapse in people with cocaine dependency. 相似文献
3.
Marc N. Branch 《Drug development research》1990,20(1):19-30
Food-deprived pigeons were trained to peck a key under either a three-component multiple random-ratio 5, random-ratio 25, random-ratio 125 schedule or a three-component multiple random-interval 10-sec, random-interval 30-sec, random-interval 125-sec schedule of food presentation. Following determination of acute effects of cocaine (1.0-13.0 mg/kg), are-sponse-rate-reducing dose was given before each daily session. Once performance under conditions of daily administration had become stable, other doses occasionally were substituted for the usual daily dose so that dose effects could be assessed. Tolerance, i.e., a rightward shift in the dose-effect curve was observed in all subjects. For subjects studied under the random-ratio schedules, however, the robustness of the tolerance usually was related to the schedule-parameter value; tolerance was great at lower random values. By contrast, subjects whose responding was maintained by random-interval schedules were less likely to show tolerance that was schedule-parameter dependent. The results also provide suggestive evidence that dose may be an important factor in determining effects of repeated cocaine exposure; repeated administration of larger doses may be less likely to result in tolerance than similar exposure to smaller doses. 相似文献
4.
Nathan R. Cleveland MD Shay Krier MD Kennon Heard MD 《Academic emergency medicine》2007,14(8):691-694
Background Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures. 相似文献
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures. 相似文献
5.
Priapism is a urologic disorder and medical emergency with a variety of known etiologies including the use of psychotropic medications. The antidepressant trazodone is the agent most frequently implicated in the precipitation of priapism. Additionally, a number of drugs of abuse including marijuana, ethanol, and cocaine have been known to cause the disorder. It is unknown if drugs may act in an additive or a synergistic manner to cause priapism. We report a case of priapism which occurred following trazodone overdose in an individual actively using cocaine. This case suggests that combined trazodone and cocaine use may pose an additional risk of priapism. Since trazodone is commonly employed as a hypnotic and often chosen for polysubstance abusers due to its low abuse potential, clinicians should be aware of the possible additive risk of priapism in this patient population. 相似文献
6.
妊娠中晚期暴露于可卡因对子代海马发育的影响 总被引:1,自引:0,他引:1
目的 建立妊娠中晚期暴露于可卡因的小鼠动物模型 ,研究可卡因对子代海马的发育是否具有影响以及这种影响在可卡因诱发的神经行为异常发病机理中可能所起的作用。方法 运用水迷宫方法观察可卡因对子鼠青春期空间辨别能力的影响 ,分别采用甲苯胺蓝染色技术和免疫组织化学结合图象分析技术观察海马中锥体细胞和神经胶质细胞的发育情况。结果 妊娠中晚期暴露于可卡因的小鼠子代在青春期海马锥体细胞极性紊乱 ,发育不良 ,未迁移到正常位置 ;神经胶质细胞数目减少。水迷宫结果显示可卡因可引起子代寻找平台的潜休期延长。结论 妊娠中晚期暴露于可卡因可引起子代青春期海马发育异常 ,这可能在可卡因引起子代空间辨别能力下降的发病机理中起着重要作用。 相似文献
7.
Kudryavtseva NN Gerrits MA Alekseenko OV Van Ree JM 《Bulletin of experimental biology and medicine》2005,140(3):320-322
Chronic injections of cocaine (20 mg/kg daily for 10 days) increase activity and decrease anxiety in male C57Bl/6j mice in
comparison with animals chronically injected with normal saline. U-50,488H (κ-opioid receptor agonist; 2.5 mg/kg) produced
an anxiolytic effect in animals preinjected with normal saline and had no effect in animals chronically injected with cocaine.
Presumably, chronic activation of dopaminergic systems caused by cocaine injections is paralleled by desensitization of k-opioid
receptor system.
__________
Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 9, pp. 305–307, September, 2005 相似文献
8.
Walker EL Ray CA Piercey MF 《Journal of neural transmission (Vienna, Austria : 1996)》1999,106(1):59-74
Summary. Although (+)-UH232 (cis-(+)-5-methoxy-1-methyl-2-(n-dipropylamino)tetralin) and (−)-DS121 (S(−)-3-(3-(cyanophenyl)-N-n-propylpiperidine)
are both preferential dopamine autoreceptor antagonists, (−)-DS121 is a more effective behavioral stimulant and dopamine releasing
agent. To further compare these two agents, Sokoloff's 2-deoxyglucose autoradiography method was used to study the effects
of (+)-UH232 and (−)-DS121 on regional brain energy metabolism. (+)-UH232, 30 mg/kg i.p., depressed metabolism in 37 of 65
brain regions and antagonized the stimulant effects of amphetamine. (−)-DS121, 30 mg/kg i.p., exhibited a strong, non-significant
trend towards an increase in regional brain energy metabolism by itself and enhanced the stimulant effects of amphetamine.
The data demonstrate dramatic differences in the effects of two autoreceptor antagonists on regional brain energy metabolism.
It is concluded that, compared to (+)-UH232, (−)-DS121 is a more effective stimulant of brain energy metabolism and autoreceptor
antagonist owing to its greater ability to increase DA release.
Received March 5, 1998; accepted June 29, 1998 相似文献
9.
Glazer Samuel S. Galanter Marc Megwinoff Olga Dermatis Helen Keller Daniel S. 《Substance Abuse》2003,24(2):93-100
The therapeutic alliance is a well-studied construct factor that is important to outcome in many forms of individual therapy. Therapeutic alliance has been rarely studied in group therapy and results in addiction treatment have been mixed. In this paper, we studied the presence of a therapeutic alliance in Network Therapy: an approach that uses peer and family support in addiction treatment. Twenty-one participants undergoing Network Therapy for cocaine addiction were observed on videotape, and were rated on therapeutic alliance using the Working Alliance Inventory and the Penn Helping Alliance Rating Scale. Results showed a significant positive correlation between therapeutic alliance and outcome as measured by the percentage of cocaine-free urine toxicology screens and by eight consecutive cocaine-free urines. 相似文献
10.
Tim Laussmann Ireneus Grzesiak Alexander Krest Kathrin Stirnat Sigrid Meier‐Giebing Uwe Ruschewitz Axel Klein 《Drug testing and analysis》2015,7(1):56-64
The chemical composition of a black powder confiscated by German customs was elucidated. Black powders are occasionally used as a ‘transporter’ for cocaine and are obviously especially designed to cloak the presence of the drug. The material consisting of cocaine, copper, iron, thiocyanate, and graphite was approached by analytical tools and chemical modelling. Graphite is added to the material probably with the intention of masking the typical infrared (IR) fingerprints of cocaine and can be clearly detected by powder X‐ray diffraction (XRD) and Raman spectroscopy. Cu2+ and NCS? ions, when carefully reacted with cocaine hydrochloride, form the novel compound (CocH)2[Cu(NCS)4] (CocH+ = protonated cocaine), which has been characterised by single crystal XRD, IR, NMR, UV/Vis absorption and EPR spectroscopy. Based on some further experiments the assumed composition of the original black powder is discussed. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献