Dissecting the Abuse Liability of Cathinone and Amphetamine Stimulants

滥用包括可卡因和甲基安非他明在内的精神兴奋剂以及 合成卡西酮药物（“浴盐”）继续在全世界和美国造成严重破坏 大多数患有兴奋剂使用障碍的人未经治疗。越 可卡因和甲基苯丙胺等已确定的兴奋剂具有高度成瘾性， 致命的，并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，合成卡西酮精神活性药物3，4-亚甲二氧基吡咯戊酮 （MDPV）、α-吡咯烷基苯丙酮（α-PVP）和相关的紧密类似物是一种高度有效且 动物模型中的有效抑制剂。这些化合物往往被用作更便宜或更 在社会经济地位较低的人口中，被监禁的个人等，努力 迄今为止， 成功了更好地了解兴奋剂依赖是如何建立的仍然至关重要 并保持，以便更好地防止兴奋剂成瘾之前，它是建立。该项目将 在大鼠模型中调查导致兴奋性药物摄入增加的情境和行为因素 静脉自我给药，与NOSI NOT-DA-21-028的目标一致。研究 根据目标I提出的建议，将确定精神兴奋剂自我给药的狂欢式获得是否 改变了在扩展访问条件下逐步增加摄入量的倾向。目标是 了解最初不受控制的消费的后果，以及这种消费是否会持续 依赖的后果。目标II下的研究将确定颅内自我刺激是否 （ICSS）奖励阈值指示了扩展访问下自我管理的升级 在一个长期存在的负强化框架的新测试中， 兴奋剂使用量不断增加最后，目标三下的调查将确定是否交替卡西酮 甲基苯丙胺的使用改变了自我给药的升级。这些新型的多药模型 将解决一个未充分研究的现象，即一些人类兴奋剂使用者替代药物 取决于成本和可用性。总之，这些拟议的研究将促进我们对 对精神刺激药物的依赖性的发展。

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.