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滥用吸入剂甲苯对小鼠产生的苯丙胺样辨别刺激效应增强。

Increases in amphetamine-like discriminative stimulus effects of the abused inhalant toluene in mice.

作者信息

Bowen Scott E

机构信息

Department of Psychology, Wayne State University, 5057 Woodward, Detroit, MI 48202, USA.

出版信息

Psychopharmacology (Berl). 2006 Jul;186(4):517-24. doi: 10.1007/s00213-006-0381-8. Epub 2006 Apr 7.

Abstract

RATIONALE

Toluene, an abused solvent, shares behavioral and pharmacological effects with abused depressant drugs. These effects include ethanol- and pentobarbital-like discriminative stimulus effects. There is also emerging evidence that this abused inhalant may share stimulus effects with abused central nervous system (CNS) stimulants.

OBJECTIVE

To further explore the discriminative stimulus effects of one abused inhalant, this experiment evaluated the amphetamine-like discriminative stimulus effects of toluene.

MATERIALS AND METHODS

Mice were trained to discriminate between d-amphetamine (1.0 mg/kg) and saline in a two-lever drug discrimination procedure in which responding was under the control of a fixed-ratio 15 schedule. Mice were tested after 10-min inhalation exposures to air or toluene (500-6,000 ppm) and stimulus generalization was examined at 0, 15, 30, 45, 60, and 75 min post-exposure.

RESULTS

Concentration-related increases in amphetamine-lever responding were observed for amphetamine doses >0.56 mg/kg with full substitution occurring immediately after testing for 1.0 and 1.78 mg/kg. Partial amphetamine-lever responding was observed for all concentrations of toluene across the 75-min post-exposure test trials. Response rates that had decreased immediately after all toluene exposures recovered within 15-min post exposure.

CONCLUSION

This partial substitution of toluene for amphetamine suggests that studies of the effects of abused solvents on brain dopaminergic systems need to be included in the study of possible CNS mechanisms.

摘要

原理

甲苯是一种被滥用的溶剂,它与被滥用的抑制性药物具有行为和药理作用。这些作用包括类似乙醇和戊巴比妥的辨别刺激作用。也有新证据表明,这种被滥用的吸入剂可能与被滥用的中枢神经系统(CNS)兴奋剂具有刺激作用。

目的

为了进一步探究一种被滥用吸入剂的辨别刺激作用,本实验评估了甲苯的苯丙胺样辨别刺激作用。

材料与方法

在两杆药物辨别程序中训练小鼠区分右旋苯丙胺(1.0毫克/千克)和生理盐水,其中反应受固定比率15程序控制。在小鼠吸入空气或甲苯(500 - 6000 ppm)10分钟后进行测试,并在暴露后0、15、30、45、60和75分钟检查刺激泛化情况。

结果

当苯丙胺剂量>0.56毫克/千克时,观察到苯丙胺杆反应随浓度增加,在测试1.0和1.78毫克/千克后立即出现完全替代。在暴露后75分钟的测试试验中,所有浓度的甲苯都观察到部分苯丙胺杆反应。所有甲苯暴露后立即下降的反应率在暴露后15分钟内恢复。

结论

甲苯对苯丙胺的这种部分替代表明,在可能的中枢神经系统机制研究中需要纳入对被滥用溶剂对脑多巴胺能系统影响的研究。

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