Accumbens firing and ultrasonic vocalizations during cocaine self-administration

可卡因自我给药期间伏隔肌发射和超声波发声

基本信息

批准号：
8450461
负责人：
David J Barker
金额：
$ 3.22万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2014-04-11
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8450461
关键词：
Abstinence Adult Affect Affective Amygdaloid structure Animal Model Animals Behavior Behavior Therapy Behavioral Blood Brain Cell Nucleus Cocaine Cocaine Dependence Development Dose Drug Addiction Drug abuse Drug usage Event Hour Intake Knowledge Lead Measurement Measures Medial Modeling Neurobiology Neurons Nucleus Accumbens Outcome Pattern Pharmaceutical Preparations Pharmacological Treatment Play Positive Reinforcer Prevention strategy Process Production Property Rattus Relapse Reporting Research Research Training Rewards Risk Factors Role Saline Satiation Self Administration Self-Administered Signal Transduction Staging Stimulus Substance abuse problem Symptoms System Testing Time Training Ultrasonics Withdrawal addiction approach avoidance behavior binge type behavior career cholinergic cue reactivity drug abuse prevention drug production drug relapse drug seeking behavior experience human subject indexing insight mesolimbic system motivational processes multidisciplinary negative mood neurochemistry prevent relating to nervous system response skills vocalization

项目摘要

DESCRIPTION (provided by applicant): The development of effective behavioral or pharmacological treatments for cocaine dependence relies on increasing our understanding of the behavioral and neural correlates of drug-seeking. Positive and negative affective states both have a reported role in the initiation of drug use (Newcomb & Felix-Ortiz 1992), bingeing behavior (Barker et al., 2010; Maier et al., 2010), withdrawal (Covington & Miczek 2003; Barros & Miczek 1996; Mutschler & Miczek 1998a; Mutschler & Miczek 1998b), or relapse (Hodgins et al., 1995). Still, studies investigating the neurobiological correlates of affect and the role affect plays in drug dependence are limited. Over the last fifteen years, the hypothesis that the affective states of rats can be reliably indexed through ultrasonic vocalizations (USVs) has received much support; 50-kHz USVs and 22-kHz USVs are consistently reported to be correlated with indices of positive and negative affective states, respectively, in adult rats in a variety of experimental paradigms. Incorporating USVs with self-administration behavior would therefore allow for a more comprehensive animal model of addiction. Preliminary results from our lab (Barker et al., 2010) suggest that doses of cocaine that prevent drug 'satiety' produce a higher ratio of negative affective USVs while those that allow animals to reach their preferred blood concentration produce a higher ratio of positive affective USVs. Research examining the neurochemistry of USV production has suggested that two separate but overlapping systems modulate 22- and 50-kHz USVs, respectively. The first of these systems-the mesolimbic dopamine system-has a purported role in the modulation of 50-kHz USVs. On the other hand, 22-kHz USVs are thought to be modulated by a second, cholinergic circuit originating in the laterodorsal tegmental nucleus (Brudzynski, 2008). One key region of overlap between these systems is the nucleus accumbens. Appropriately, eletrophysiological and neurochemical evidence has also implicated the NAcc in processing appetitive and aversive outcomes (e.g. Wheeler et al., 2008) as well as facilitating approach and avoidance behaviors (e.g. Rada & Hoebel, 2001; Hoebel, Avena, & Rada, 2007) To further investigate the neural substrates of affective processing during self-administration, as well as the role that affect plays in the reinstatement of drug-seeking behavior, we will record ultrasonic vocalizations, and the firing of NAcc core and medial shell neurons during a zero dose saline condition, two self-administered cocaine doses, and tests of reinstatement.

描述（由申请人提供）：针对可卡因依赖的有效行为或药物治疗的开发依赖于增加我们对药物寻求的行为和神经相关性的理解。据报道，积极和消极情感状态在开始吸毒（Newcomb & Felix-Ortiz 1992）、暴饮行为（Barker et al., 2010; Maier et al., 2010）、戒断（Covington & Miczek 2003;巴罗斯和米切克 1996；穆茨勒和米切克 1998a； Miczek 1998b），或复发（Hodgins 等，1995）。尽管如此，调查情感的神经生物学相关性以及情感在药物依赖中所起的作用的研究仍然有限。在过去的十五年里，老鼠的情感状态可以通过超声波发声（USV）可靠地索引的假设得到了很多支持。据报道，在各种实验范式中，50 kHz USV 和 22 kHz USV 分别与成年大鼠的积极和消极情感状态指数相关。因此，将 USV 与自我管理行为结合起来将有助于建立更全面的成瘾动物模型。我们实验室的初步结果（Barker et al., 2010）表明，防止药物“饱腹感”的可卡因剂量会产生更高比例的负面情感 USV，而那些允许动物达到其首选血液浓度的剂量会产生更高比例的正面情感 USV。 USV。检查 USV 产生的神经化学的研究表明，两个独立但重叠的系统分别调制 22 kHz 和 50 kHz USV。其中第一个系统——中脑边缘多巴胺系统——据称在 50kHz USV 的调制中发挥着作用。另一方面，22kHz USV 被认为是由源自背侧被盖核的第二个胆碱能电路调制的（Brudzynski，2008）。这些系统之间重叠的一个关键区域是伏隔核。适当地，电生理学和神经化学证据也表明 NAcc 参与处理食欲和厌恶结果（例如 Wheeler 等人，2008 年）以及促进接近和回避行为（例如 Rada 和 Hoebel，2001 年；Hoebel、Avena 和 Rada，2007 年））进一步研究自我管理过程中情感处理的神经基础，以及由于情感在寻求药物行为的恢复中所起的作用，我们将记录超声波发声，以及在零剂量盐水条件下、两次自我注射可卡因剂量和恢复测试期间 NAcc 核心和内侧壳神经元的放电。