Dissecting the Abuse Liability of Cathinone and Amphetamine Stimulants

滥用精神运动兴奋剂，包括可卡因和甲基苯丙胺，以及 合成卡西酮类药物(“浴盐”)继续在全世界和美国肆虐。 美国，大多数患有兴奋剂使用障碍的人得不到治疗。越多 像可卡因和甲基苯丙胺这样的老牌兴奋剂具有很强的成瘾性，可能会严重上瘾 这是致命的，可能导致长期的大脑改变，对健康和福祉有许多影响。 最近的研究表明，合成卡西酮类精神活性药物3，4-亚甲基二氧吡咯丙酮 (Mdpv)、α-吡咯烷基戊二酮(α-pvp)及其类似物是一种高效的 动物模型中的有效增强剂。这些化合物往往被用作更便宜或更多的 较低社会经济人口中的可用替代品、被监禁的个人等 开发小分子或疫苗疗法治疗精神运动兴奋剂依赖，到目前为止， 成功了。更好地了解兴奋剂依赖是如何建立的仍然是至关重要的 并加以维护，以便更好地在兴奋剂成瘾建立之前防止它。这个项目将 研究环境和行为因素对大鼠刺激性药物依赖升级的影响 静脉自我给药，与NOSI NOT-DA-21-028的目标一致。研究 根据AIM提出的建议，我将确定是否像狂欢一样获得精神刺激性自我管理 改变在延长通道条件下增加摄入量的倾向。我们的目标是 了解最初不受控制的消费的后果，以及这种情况是否会持续 依赖的后果。AIM II下的研究将确定脑内自我刺激是否 (ICSS)奖励阈值索引扩展访问下的自我管理升级 在一项对长期存在的负面强化理解框架的新测试中， 兴奋剂使用不断升级。最后，AIM III项下的调查将确定替代卡西诺酮 甲基苯丙胺的使用改变了自我管理的升级。这些新的多药模型 将解决一个未被充分研究的现象，即一些人类兴奋剂使用者替代药物 取决于成本和可获得性。总而言之，这些拟议的研究将增进我们对 精神运动兴奋剂依赖的发展。

The abuse of psychomotor stimulants, including cocaine and methamphetamine, as well as the synthetic cathinone drugs (“bathsalts”), continues to wreak havoc worldwide and in the United States of America, with most individuals that suffer with stimulant use disorders going untreated. The more established stimulants such as cocaine and methamphetamine are highly addictive, can be acutely lethal and can result in long-term brain alterations with many implications for health and well-being. Recent studies show that synthetic cathinone psychoactive drugs 3,4-methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP) and associated close analogs are a highly potent and efficacious reinforcers in animal models. These compounds tend to be used as cheaper or more available substitutes in lower socioeconomic populations, by incarcerated individuals, etc. Efforts to develop small molecule or vaccine therapies for psychomotor stimulant dependence have not, as yet, succeeded. It continues to be critical to better understand how stimulant dependence is established and maintained so as to better prevent stimulant addiction before it is established. This project will investigate the situational and behavioral contributors to escalating stimulant drug taking in rat models of intravenous self-administration, consistent with the goals of NOSI NOT-DA-21-028. Studies proposed under Aim I will determine if binge-like acquisition of psychostimulant self-administration alters the propensity for escalated intake under extended access conditions. The goal is to understand the consequences of initial uncontrolled consumption and whether that has lasting consequences for dependence. Studies under Aim II will determine if the intra-cranial self-stimulation (ICSS) reward threshold indexes the escalation in self-administration under extended access conditions, in a novel test of a longstanding negative-reinforcement framework for understanding escalating stimulant use. Finally, investigations under Aim III will determine if alternating cathinone and methamphetamine use alters the escalation of self-administration. These novel poly-drug models will address an understudied phenomenon whereby some human stimulant users substitute drugs depending on cost and availability. In total, these proposed studies will advance our understanding of the development of dependence on psychomotor stimulant drugs.