Ontogeny of behavioral sensitization: associative and nonassociative processes

行为敏化的个体发生：联想和非联想过程

基本信息

批准号：
8067107
负责人：
Sanders McDougall
金额：
$ 24.03万
依托单位：
CALIFORNIA STATE UNIV SAN BERNARDINO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8067107
关键词：
Accounting Acute Adult Age Amphetamines Amygdaloid structure Anesthesia procedures Applications Grants Area Attenuated Basal Ganglia Behavioral Bilateral Brain Brain region Cell Nucleus Cocaine Cues Data Data Quality Development Doctor of Philosophy Dopamine Dorsal Drug Addiction Educational process of instructing Environment Exhibits Exploratory/Developmental Grant Exposure to FOS gene Food Services Funding Future Goals Grant Growth Home environment Housing Immediate-Early Genes Industry Infusion procedures Injection of therapeutic agent Institution Isoflurane Journals Knowledge Laboratories Laboratory Research Lidocaine Limb structure Manuscripts Measures Mediating Mentors Microdialysis Microinjections Mus Nucleus Accumbens Occupations Opioid Paper Pattern Pharmaceutical Preparations Play Positioning Attribute Prefrontal Cortex Procedures Process Productivity Publications Publishing Rattus Research Research Personnel Research Project Grants Role Saline Side Structure of terminal stria nuclei of preoptic region Students System Testing Time Training Ventral Tegmental Area Wages Work Writing age related anterior commissure area striata base behavioral sensitization career classical conditioning conditioning immunoreactivity in vivo inhibitor/antagonist insight interstitial neuromechanism novel professor programs psychostimulant public health relevance regional difference relating to nervous system research study response symposium tool waiver young adult

项目摘要

DESCRIPTION (provided by applicant): Repeated exposure to psychostimulant drugs (e.g., cocaine) results in the related phenomena of behavioral sensitization and conditioned activity. In adult rats, both associative and nonassociative processes are important for these phenomena, although the brain regions that mediate these processes are uncertain. Young rats, on the other hand, do not show adult-like behavioral sensitization and conditioned activity. This fact is most evident when drug pretreatment occurs on a single day (i.e., the "one-shot" paradigm). Specifically, adult rats will exhibit conditioned activity and context-dependent, but not context-independent, sensitization after a single cocaine pretreatment; whereas, young rats show robust context-dependent and context-independent sensitization and no conditioned activity. To account for this pattern of results, we have hypothesized that a single psychostimulant exposure neither initiates an excitatory associative process in young rats (i.e., accounting for the lack of conditioned activity) nor does it initiate an inhibitory associative process (i.e., accounting for the occurrence of context-independent sensitization). The purpose of this grant proposal is to distinguish the neural mechanisms underlying context-dependent and context-independent sensitization and conditioned activity. Both adult and young rats will be studied because age-dependent differences in behavioral sensitization and conditioned activity can be used as a tool for further elucidating the neural mechanisms underlying these phenomena. The purpose of the initial experiments is to (a) determine what environmental cues, if any, are necessary for young rats to exhibit behavioral sensitization (Specific Aim 1), and (b) determine the persistence of "one-shot" behavioral sensitization and conditioned activity in young and adult rats (Specific Aim 2). The neural bases of behavioral sensitization will be examined by measuring regional differences in Fos immunoreactivity after completion of conditioned activity and sensitization testing (Specific Aim 3). The pattern of Fos immunoreactivity is hypothesized to differ according to age, with only adult rats predicted to show increased Fos immunoreactivity in brain areas mediating associative components of behavioral sensitization and conditioned activity. Second, lidocaine will be microinjected into various brain regions of adult and young rats to determine whether neural mechanisms underlying the associative and nonassociative components of behavioral sensitization and conditioned activity can be parsed apart (Specific Aim 4). Third, PKC is important for associative learning so Specific Aim 5 will determine whether a PKC inhibitor (chelerythrine) will attenuate associative and/or nonassociative components of behavioral sensitization and conditioned activity in young and adult rats. Results from these various experiments will significantly enhance our knowledge concerning the ontogeny of behavioral sensitization and provide additional insight about the neural mechanisms underlying the associative and nonassociative components of behavioral sensitization and conditioned activity. Public Health Relevance: Exposure to psychostimulant drugs (e.g., cocaine and amphetamine) produces behavioral sensitization and conditioned activity. Sensitization-related changes in various brain systems may play an important role in drug addiction. The purpose of this grant proposal is to assess the importance of associative learning, and related neural changes, involved in the development and persistence of behavioral sensitization and conditioned activity in young and adult rats.

描述（由申请人提供）：反复接触精神刺激药物（例如可卡因）导致行为敏化和条件活性的相关现象。在成年大鼠中，尽管不确定介导这些过程的大脑区域尚不确定，但缔合和非社交过程对这些现象都很重要。另一方面，年轻的大鼠不会表现出成人样的行为敏感和条件活性。当药物预处理发生在一天中（即“一击”范式）时，这一事实最为明显。具体而言，成年大鼠将在单一可卡因预处理后表现出条件活性和上下文依赖性但不依赖上下文的敏化。鉴于，年轻的大鼠表现出强大的上下文依赖性和与上下文无关的敏感性，没有条件活动。为了说明这种结果模式，我们假设单一的心理刺激暴露都不启动年轻大鼠的兴奋性缔合过程（即考虑到条件活动缺乏活动），也不启动抑制性缔合过程（即，考虑到与上下文无关依赖性敏感性的发生）。这项赠款提案的目的是区分背景依赖性和无上下文独立的敏感性和条件活动的神经机制。将研究成年大鼠，因为行为敏化和条件活性的年龄依赖性差异可以用作进一步阐明这些现象的神经机制的工具。最初实验的目的是（a）确定年轻大鼠表现出行为敏化的必要环境提示（特定目标1），以及（b）确定年轻大鼠和成年大鼠的“一击”行为敏化和条件活性的持久性（特定目标2）。行为敏化的神经基础将通过测量条件活性和致敏测试完成后FOS免疫反应性的区域差异来检查（特定目标3）。假设FOS免疫反应性的模式根据年龄而有所不同，只有成年大鼠预计在介导行为敏感性和条件活性的关联成分的大脑区域的FOS免疫反应性增加。其次，利多卡因将对成年大鼠和年轻大鼠的各个大脑区域进行显微注射，以确定行为敏化和条件活性的关联和非社交成分背后的神经机制是否可以分开（特定目标4）。第三，PKC对于联想学习很重要，因此特定的目标5将确定PKC抑制剂（Chelerythrine）是否会减弱行为敏化和适应年轻大鼠的行为敏化和条件活性的联想和/或非缔合成分。这些各种实验的结果将显着增强我们关于行为敏化本体的知识，并提供有关行为敏化和条件活性的关联和非缔合成分的神经机制的更多见解。公共卫生相关性：暴露于心理刺激药物（例如可卡因和苯丙胺）会产生行为敏感和条件活动。各种大脑系统中与敏化相关的变化可能在药物成瘾中起重要作用。这项赠款提案的目的是评估关联学习的重要性以及与行为敏感性发展和持续性的相关神经变化的重要性以及年轻大鼠和成年大鼠的条件活动的持久性。