Behavioral Effects of Dissociatives in Adolescents: Comparison with Adults

描述（由申请人提供）：本研究的广泛目标是更好地了解解离的行为影响，特别关注其在青少年中的影响。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，但越来越多地以亚麻醉剂量用于临床和非临床目的。这些药物已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两种主要的精神疾病，精神分裂症和重度抑郁症。此外，有证据表明，亚麻醉剂量的解离剂在疼痛治疗中是有用的。分离性药物也是一种重要的滥用药物，通常被归类为“俱乐部药物”。 分离型人格对青少年特别重要。这些药物经常被青少年在舞蹈俱乐部或“锐舞”场所使用。调查研究表明，近年来青少年使用解离剂的情况有所增加，而且开始使用的年龄有所下降。五氯苯酚和氯胺酮以及非处方止咳药美沙芬都是如此。尽管如此，还没有发表的研究系统地研究了青少年和成年人在解离行为影响方面的差异。 目前的项目将比较解离性药物（包括氯胺酮，PCP和二甲双胍）对青少年和成年实验室大鼠的行为影响。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。致敏是重复使用后药物作用的增加，并且被认为对成瘾的发展很重要。本研究的具体目的是：1）比较青少年和成年大鼠中解离性物质的急性行为效应; 2）比较青少年和成年大鼠中解离性物质致敏的发展; 3）评估谷氨酸释放在青少年和成年大鼠中解离性物质行为效应中的作用;（4）比较青春期和成年大鼠血浆中游离物质的浓度。总之，这项研究将有助于更好地了解青少年和成年人解离的影响，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。

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.