Behavioral Effects of Dissociatives in Adolescents: Comparison with Adults

青少年分离性行为的影响：与成人的比较

• 批准号: 7901553
• 负责人: KEITH A TRUJILLO
• 金额: $ 11.1万
• 依托单位: CALIFORNIA STATE UNIVERSITY SAN MARCOS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901553
• 关键词: Acute; Adolescence; Adolescent; Adult; Affect; Age; Anesthetics; Animal Model; Antidepressive Agents; Ataxia; Attention; Behavioral; Chronic; Clinical; Clinical Research; Coughing; Dancing; Development; Dextromethorphan; Dose; Drug abuse; Drug usage; Glutamates; Goals; Human; Ketamine; Knowledge; Laboratories; Laboratory Animal Models; Laboratory Animals; Laboratory Rat; Lead; Life; Link; Major Depressive Disorder; Mental Depression; Mental disorders; Modeling; Pain; Pharmaceutical Preparations; Phencyclidine; Physiological; Plasma; Prevention; Psychotropic Drugs; Publishing; Rattus; Research; Role; Schizophrenia; Surveys; Syndrome; Teenagers; Time; Work; addiction; base; behavioral sensitization; club drug; drug of abuse; inhibitor/antagonist; interest; pre-clinical; response; stereotypy

DESCRIPTION (provided by applicant): The broad goal of this research is to better understand the behavioral effects of dissociatives, with a particular focus on their effects in adolescents. Dissociatives, including phencyclidine (PCP) and ketamine were originally developed as anesthetics, but are being increasingly used at subanesthetic doses for both clinical and non-clinical purposes. These drugs have been used in human clinical studies and preclinical animal models to better understand and treat two major psychiatric disorders, schizophrenia and major depression. In addition, evidence indicates that subanesthetic doses of dissociatives are useful in the treatment of pain. Dissociatives are also an important class of abused drugs, often classified as 'club drugs'. Dissociatives are of special interest and importance to adolescents. These drugs are often used by teens in dance club or "rave" settings. Survey research shows increased use of dissociatives by teens in recent years, as well as decreased age for initiation of use. This is true for both PCP and ketamine, as well as the over-the-counter cough suppressant, dextromethorphan. Despite all of this, no published research has systematically examined differences between adolescents and adults in the behavioral effects of dissociatives. The current project will compare the behavioral effects of dissociatives (including ketamine, PCP and dextromethorphan) in adolescent and adult laboratory rats. In addition to examining differences in the acute response to these drugs, the studies will also explore differences following repeated administration, and in particular, a phenomenon known as behavioral sensitization. Sensitization is an increase in an effect of a drug following repeated use, and is thought to be important to the development of addiction. The following specific aims will be examined: 1) to compare the acute behavioral effects of dissociatives in adolescent and adult rats; 2) to compare the development of sensitization to dissociatives in adolescent and adult rats; 3) to assess the role of glutamate release in the behavioral effects of dissociatives in adolescent and adult rats; and 4) to compare the plasma concentrations of dissociatives in adolescent and adult rats. Together, the research will lead to a better understanding of the effects of dissociatives in adolescents and adults, and may lead to better treatments for schizophrenia, depression, pain and drug abuse.

描述(由申请人提供)：这项研究的广泛目标是更好地了解分离者的行为影响，特别是他们对青少年的影响。解离剂，包括苯环利定(PCP)和氯胺酮，最初是作为麻醉剂开发的，但越来越多地被用于临床和非临床目的的亚麻醉剂量。这些药物已被用于人类临床研究和临床前动物模型，以更好地了解和治疗精神分裂症和抑郁症这两种主要精神疾病。此外，有证据表明，麻醉下剂量的解离药在治疗疼痛方面是有用的。分离性药物也是一类重要的滥用药物，通常被归类为“俱乐部毒品”。 青少年对孤独症特别感兴趣，也很重要。这些药物经常被青少年在舞厅或“狂欢派对”场所使用。调查研究表明，近年来青少年使用解离药物的人数增加，开始使用解离药物的年龄也有所下降。五氯苯酚和氯胺酮以及非处方药右美沙芬都是如此。尽管如此，还没有发表的研究系统地检查青少年和成年人在分离的行为影响方面的差异。 目前的项目将比较解离剂(包括氯胺酮、五氯苯酚和右美沙芬)对青少年和成年实验大鼠的行为影响。除了检查对这些药物的急性反应的差异外，这些研究还将探索重复给药后的差异，特别是一种被称为行为敏化的现象。致敏是药物在反复使用后效果的增强，被认为对成瘾的发展很重要。研究的具体目标如下：1)比较青春期和成年大鼠对解离剂的急性行为影响；2)比较青春期和成年大鼠对解离剂的敏化发展；3)评估谷氨酸释放在青春期和成年大鼠行为效应中的作用；以及4)比较青春期和成年大鼠血浆中解离剂的浓度。总而言之，这项研究将使人们更好地了解分离者对青少年和成年人的影响，并可能导致更好地治疗精神分裂症、抑郁症、疼痛和药物滥用。