Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71103, United States.
Drug Alcohol Depend. 2013 Dec 1;133(2):405-12. doi: 10.1016/j.drugalcdep.2013.06.025. Epub 2013 Jul 26.
We have previously reported that combining low doses of oxazepam and metyrapone (OX/MET) reduces intravenous cocaine self-administration without affecting stress-hormone levels. We hypothesized that the combination of OX/MET would also inhibit the reinstatement of cocaine or methamphetamine seeking induced by the presentation of a conditioned reinforcer and that stress hormone levels would not be influenced by this treatment.
Male rats were implanted with jugular catheters and trained to self-administer cocaine or methamphetamine during daily 2-h sessions. During training, cocaine or methamphetamine delivery was paired with the presentation of a tone and the illumination of a house light. Following stable self-administration, rats were placed into forced abstinence. During cue-reactivity testing, rats were placed back into the operant chambers and responding only resulted in the presentation of the conditioned reinforcer; no cocaine or methamphetamine was delivered. Blood was collected on the last day of self-administration and on the day of cue-reactivity testing (either 15-min or 2-h session) to assess plasma corticosterone.
The response-contingent presentation of the conditioned reinforcer reliably maintained cocaine or methamphetamine seeking following vehicle pretreatment. Pretreatment with OX/MET resulted in a dose-related attenuation of both cocaine and methamphetamine seeking. Corticosterone levels were significantly different at the end of the 15-min session, but not following the 2-h session.
These data suggest that OX/MET may be useful in blocking the ability of environmental cues to stimulate both cocaine and methamphetamine seeking and that this effect is not entirely dependent on stress hormone levels.
我们之前曾报道，联合使用低剂量的奥沙西泮和米替拉酮（OX/MET）可减少静脉内可卡因的自我给药，而不会影响应激激素水平。我们假设，OX/MET 的联合使用也会抑制由条件性强化物引起的可卡因或甲基苯丙胺觅药的复燃，并且这种治疗不会影响应激激素水平。
雄性大鼠被植入颈静脉导管，并在每日 2 小时的时段内接受可卡因或甲基苯丙胺的自我给药训练。在训练期间，可卡因或甲基苯丙胺的输送与呈现音调以及点亮房屋灯光配对。在稳定的自我给药之后，大鼠被置于强制禁欲状态。在线索反应性测试期间，大鼠被放回操作箱中，只有在呈现条件性强化物时才会产生反应；不会输送可卡因或甲基苯丙胺。在自我给药的最后一天和线索反应性测试的那天（15 分钟或 2 小时的时段）采集血液，以评估血浆皮质酮。
条件性强化物的反应依赖性呈现可靠地维持了药物预处理后的可卡因或甲基苯丙胺觅药。OX/MET 的预处理导致可卡因和甲基苯丙胺觅药呈剂量相关衰减。皮质酮水平在 15 分钟的时段结束时显著不同，但在 2 小时的时段后没有差异。
这些数据表明，OX/MET 可能有助于阻断环境线索刺激可卡因和甲基苯丙胺觅药的能力，并且这种作用不完全依赖于应激激素水平。
