Zhang Xiang-Yang, Kosten Therese A
Division of Substance Abuse, Yale University School of Medicine, VA-CT Hospital System, West Haven, CT 06516, USA.
Neuropsychopharmacology. 2007 Mar;32(3):638-45. doi: 10.1038/sj.npp.1301120. Epub 2006 Jun 14.
Noradrenergic transmission is implicated in the biochemical and behavioral effects of cocaine. Recently, we demonstrated that the alpha 1-adrenergic receptor antagonist prazosin attenuates cocaine-induced reinstatement of drug-seeking behavior. We now assessed whether prazosin could counter the effect of previous exposure to cocaine to enhance subsequent self-administration behavior. Rats were pre-exposed to systemic injections of either saline, prazosin (0.3 mg/kg), saline+cocaine (10 mg/kg), or prazosin+cocaine for 5 days. Starting 15-18 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.5 mg/kg/infusion) under a fixed ratio 3 (FR3) schedule of reinforcement. Several tests were conducted. First, responding for cocaine under an FR3 schedule was assessed across several doses (0.125-1.0 mg/kg/infusion). Second, responding for cocaine (0.5 mg/kg/infusion) under a progressive-ratio (PR) schedule was examined for 6 consecutive days. Finally, responding for cocaine (0, 0.5, and 1.0 mg/kg/infusion) was determined under the PR schedule of reinforcement. Results showed that cocaine pre-exposed rats self-administer more cocaine compared to saline pre-exposed rats when tested under both the FR and PR schedules. Rats pre-exposed to cocaine plus prazosin did not show enhanced cocaine self-administration. These rats, as well those pre-exposed to prazosin alone, showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, previous exposure to cocaine enhanced cocaine self-administration, an effect that appears to involve activation of alpha 1-adrenergic receptors. These data, along with several recent studies, show further support for the contribution of noradrenergic transmission in the behavioral effects of cocaine.
去甲肾上腺素能传递与可卡因的生化及行为效应有关。最近，我们证明了α1 - 肾上腺素能受体拮抗剂哌唑嗪可减弱可卡因诱导的觅药行为复燃。我们现在评估哌唑嗪是否能对抗先前接触可卡因对增强后续自我给药行为的影响。将大鼠分为四组，分别连续5天进行如下预处理：全身注射生理盐水、哌唑嗪（0.3毫克/千克）、生理盐水 + 可卡因（10毫克/千克）或哌唑嗪 + 可卡因。在最后一次预处理注射后的15 - 18天开始，训练大鼠在固定比率3（FR3）强化程序下自我给药可卡因（0.5毫克/千克/输注）。进行了多项测试。首先，评估在FR3程序下不同剂量（0.125 - 1.0毫克/千克/输注）的可卡因给药反应。其次，连续6天检查在累进比率（PR）程序下对可卡因（0.5毫克/千克/输注）的反应。最后，在PR强化程序下测定对可卡因（0、0.5和1.0毫克/千克/输注）的反应。结果表明，在FR和PR程序测试中，与生理盐水预处理的大鼠相比，可卡因预处理的大鼠自我给药的可卡因更多。预先接触可卡因加哌唑嗪的大鼠未表现出增强的可卡因自我给药行为。这些大鼠以及仅预先接触哌唑嗪的大鼠，其可卡因自我给药水平与生理盐水预处理的大鼠相似。因此，先前接触可卡因会增强可卡因自我给药，这种效应似乎涉及α1 - 肾上腺素能受体的激活。这些数据以及最近的几项研究，进一步支持了去甲肾上腺素能传递在可卡因行为效应中的作用。
