首页> 外文期刊>Neuropsychopharmacology >Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization
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Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

机译:哌醋甲酯可增强大鼠尼古丁与滥用有关的行为效应:静脉内自我给药,药物歧视和运动交叉敏化。

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Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague–Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03?mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25–10?mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5?mg/kg) or saline before 12 consecutive nicotine (0.03?mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03–0.3?mg/kg) and methylphenidate (1.25–10?mg/kg), alone and in combination with a low nicotine dose (0.056?mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5?mg/kg) was tested in rats previously treated with nicotine (0.2–0.8?mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.
机译:在受控的人体实验室实验中,包括D-苯异丙胺,可卡因和哌醋甲酯在内的兴奋剂会增加吸烟。尽管尚不清楚这种作用的潜在机制,但兴奋剂有可能直接增强尼古丁与滥用有关的作用。在本研究中,我们表征了哌醋甲酯和尼古丁在静脉内自我给药,药物区分和运动交叉敏化程序中的行为药理相互作用。训练成年雄性Sprague–Dawley大鼠对静脉内尼古丁(0.01或0.03?mg / kg /输注)或蔗糖有反应,并测定哌醋甲酯(1.25–10?mg / kg)的急性作用。此外,在连续12次尼古丁(0.03微克/千克/输注)自我给药之前,分别给不同组的大鼠用哌醋甲酯(2.5微克/千克)或生理盐水治疗。接下来,分别在尼古丁中测试烟碱(0.03–0.3?mg / kg)和哌醋甲酯(1.25–10?mg / kg)的歧视性刺激作用,并与低烟碱剂量(0.056?mg / kg)组合使用训练的大鼠。最后,在先前用尼古丁(0.2–0.8?mg / kg)治疗的大鼠中测试了重复的哌醋甲酯(2.5?mg / kg)的运动效果。结果表明,在减少蔗糖维持的反应剂量下,急性哌醋甲酯增加了尼古丁的自给率。此外,重复使用哌醋甲酯后对该作用的耐受性不明显。哌醋甲酯虽然不能单独替代尼古丁,但剂量依赖性地增强了低尼古丁剂量的歧视性刺激作用。另外,反复的尼古丁暴露促进了运动致敏剂哌醋甲酯的发展。结合最近的临床发现,这些结果表明哌醋甲酯可能增强尼古丁与滥用有关的行为影响,也许增加对烟草依赖的脆弱性。

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