Bespalov Anton, Sukhotina Irina, Medvedev Ivan, Malyshkin Andrey, Belozertseva Irina, Balster Robert, Zvartau Edwin
Department of Psychopharmacology, Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197089, Russia.
Pharmacol Biochem Behav. 2003 Apr;75(1):199-208. doi: 10.1016/s0091-3057(03)00071-6.
Animal models are needed to study the abuse-related behavioral and pharmacological effects of inhaled solvents. Previous studies have suggested that intracranial self-stimulation techniques may be successfully adapted for testing the effects of solvent exposure. The present study aimed to assess the effects of toluene, cyclohexane, acetone, and petroleum benzine (a widely used mixture of hexanes and heptanes) in rats trained to lever press or nose-poke for electrical stimulation delivered through electrodes implanted into the medial forebrain bundle. It was found that toluene, cyclohexane, and benzine but not acetone, increased rates of responding, particularly at the lower stimulation intensities. In another set of experiments utilizing an auto-titration procedure, all tested solvents significantly reduced self-stimulation thresholds. However, only for toluene and benzine were these effects observed at the exposure levels that did not impair rates of operant performance. There may not be such a clear separation of effects for acetone and cyclohexane. Thus, toluene and benzine appear to selectively affect brain reward systems in a manner similar to that for most other abused drugs. Data from intracranial self-stimulation studies of solvents may be useful in abuse potential assessment of individual compounds and for examining neural and behavioral processes involved in inhalant abuse.
需要动物模型来研究吸入性溶剂与滥用相关的行为和药理作用。先前的研究表明,颅内自我刺激技术可能成功适用于测试溶剂暴露的影响。本研究旨在评估甲苯、环己烷、丙酮和石油苯(一种广泛使用的己烷和庚烷混合物)对经训练通过植入内侧前脑束的电极进行杠杆按压或鼻触以获得电刺激的大鼠的影响。研究发现,甲苯、环己烷和苯但不是丙酮,会增加反应率,尤其是在较低的刺激强度下。在另一组使用自动滴定程序的实验中,所有测试的溶剂都显著降低了自我刺激阈值。然而,只有甲苯和苯在不损害操作性行为表现率的暴露水平下观察到这些效果。丙酮和环己烷可能没有如此明显的效果区分。因此,甲苯和苯似乎以与大多数其他滥用药物类似的方式选择性地影响脑奖赏系统。来自溶剂颅内自我刺激研究的数据可能有助于评估单个化合物的滥用潜力,并用于研究吸入剂滥用所涉及的神经和行为过程。