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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Drug-free and context-dependent locomotor hyperactivity in DBA/2 J mice previously treated with repeated cocaine: Relationship with behavioral Sensitization and role of noradrenergic receptors
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Drug-free and context-dependent locomotor hyperactivity in DBA/2 J mice previously treated with repeated cocaine: Relationship with behavioral Sensitization and role of noradrenergic receptors

机译：先前用反复可卡因治疗的DBA / 2 J小鼠的无毒和上下文的运动量多动：与非肾上腺素能受体的行为致敏和作用的关系

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摘要

Drug-associated contexts and discrete cues can trigger motivational states responsible for drug-seeking behavior and relapse. In preclinical research, drug-free conditioned hyperactivity has been used to investigate the expression of memories associated with psychostimulant drug effects. Addictive drugs can produce long-lasting sensitization to their psychomotor actions, a phenomenon known as behavioral sensitization. The neuroplasticity underlying behavioral sensitization appears to be involved in pathological drug pursuit and abuse. In the present study we evaluated drug-free, context-dependent hyperactivity in DBA/2 J mice previously treated with cocaine and we explored whether this conditioned effect was related to behavioral sensitization. Given the role of noradrenergic (NA) neurotransmission in memory retrieval, consolidation and reconsolidation processes, we also investigated whether conditioned hyperactivity in a drug-free state was mediated by NA receptors. Animals underwent a sensitization protocol with six cocaine injections (0, 5, 10 or 20 mg/kg) paired to a particular floor cue. Three days after this sensitization phase, all animals were exposed to the same familiar floor environment without drug treatment. A second test with an unfamiliar floor was conducted 24 h later. Conditioned hyperactivity was also explored after one or three cocaine pairings and was evaluated for its duration (with repeated familiar vs. unfamiliar floor tests). In a series of pharmacological experiments, we evaluated the effects propranolol (a non-selective antagonist of beta 1- and beta 2-receptors) and prazosin (alpha 1-receptor antagonist) on conditioned hyperactivity. Cocaine treatment produced both robust sensitization and drug-free conditioned hyperactivity, an effect that lasted up to 17 days (with cocaine 20 mg/kg). A significant correlation between the magnitude of cocaine sensitization and the level of conditioned hyperactivity was found. Propranolol, but not prazosin, blocked context-dependent hyperlocomotion in a drug-free state. Our data, together with a vast body of literature, indicate that the NA system plays a key role in the retrieval and behavioral expression of drug-associated memories.
机译：药物相关的背景和离散线索可以引发负责药物寻求行为和复发的励志状态。在临床前研究中，无药物调节多动症已经用于研究与精神潜能药物影响相关的记忆的表达。上瘾的药物可以产生持久的敏感性敏感性，这是一种称为行为致敏的现象。行为致敏的神经塑性似乎涉及病理药物追求和滥用。在本研究中，我们在先前用可卡因治疗的DBA / 2 J小鼠中评估无毒的上下文依赖的多动，我们探讨了这种调节效果是否与行为敏化有关。鉴于Notadrenergic（Na）神经递血在记忆检索，固结和再氧化过程中的作用，我们还研究了无药物状态的病理过度活性是否由Na受体介导。动物经历了六种可卡因注射（0,5,10或20mg / kg）与特定地板提示的致敏协议。在这种敏感阶段三天后，所有动物都暴露于同一熟悉的地板环境，没有药物治疗。与陌生地板的第二次测试以后进行了24小时。在一个或三个可卡因配对之后还探讨了调节的多动，并评估其持续时间（重复熟悉的与不熟悉的地板测试）。在一系列药理实验中，我们评估了丙烯醇（β1-和β2-受体的非选择性拮抗剂）和Prazosin（α1-受体拮抗剂）的效果。可卡因治疗产生稳健的致敏和无毒调理过度，持续17天的效果（可卡因20mg / kg）。发现可卡因敏化程度与条件多动水平之间的显着相关性。普萘洛尔，但不是Prazosin，在无毒状态下阻止了依赖于上下文的血管流动性。我们的数据与庞大的文献一起表明NA系统在药物相关存储器的检索和行为表达中起着关键作用。

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