Bath salts: abuse-related and toxic effects

浴盐：滥用相关和毒性作用

• 批准号: 9015423
• 负责人: Gregory Thomas Collins
• 金额: $ 33.97万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9015423
• 关键词: Abstinence; Acute; Animal Model; Bathing; Behavior; Blood Pressure; Caffeine; Cardiovascular system; Cessation of life; Chemicals; Cues; Designer Drugs; Development; Dopamine; Dose; Drug abuse; Effectiveness; Health; Heart Rate; Hypertension; Internet; Knowledge; Legal; Marketing; Nature; Overdose; Pharmaceutical Preparations; Preparation; Procedures; Property; Psychotropic Drugs; Radio; Rattus; Recording of previous events; Reinforcement Schedule; Relapse; Research; Salts; Schedule; Self Administration; Self-Administered; Serotonin; Stimulus; Tachycardia; Telemetry; Testing; Toxic effect; base; cathinone; compare effectiveness; craving; dopamine transporter; drug seeking behavior; effective therapy; inhibitor/antagonist; innovation; khat; monoamine; neuropsychiatry; noradrenaline transporter; novel; reinforcer; response; serotonin transporter; synthetic drug

 DESCRIPTION (provided by applicant): The past 5 years have seen a dramatic increase in the abuse of synthetic cathinones (e.g., MDPV and methylone), which are marketed as "bath salts," and are widely available for purchase on the internet and in local shops as "safe" and "legal highs." In addition to a high potential for abuse, "bath salts" also have a high potential fr toxicity, characterized by severe cardiovascular and neuropsychiatric complications. Although the mechanisms that contribute to these high rates of abuse and toxicity are currently unclear, it is important to note that "bath salts" are most often mixtures of multiple psychoactive drugs, including mixtures of two different synthetic cathinones, or mixtures of a synthetic cathinone and caffeine. This proposal consists of three independent aims focused on comparing the reinforcing effectiveness, relapse-related behaviors, and toxic effects of "bath salts" mixtures (MDPV + methylone, MDPV + caffeine, and methylone + caffeine) with those of synthetic cathinones alone (MDPV and methylone). This project combines well-established animal models of abuse (self-administration) and toxicity (cardiovascular recordings) with isobolographic analysis to evaluate the highly innovative hypotheses that common "bath salts" mixtures are (1) more potent and effective reinforcers than synthetic cathinones alone; (2) more effective at strengthening drug-stimuli associations involved in relapse than synthetic cathinones alone; and (3) more potent and effective at producing tachycardia and hypertension as well as other features of the "bath salts" toxidrome than synthetic cathinones alone. Together, the results of the proposed studies will provide essential information about factors that contribute to the high rates of "bath salts" abuse and toxicity. This new knowledge will guide development of novel and targeted treatments for the ever-increasing and evolving problem of "bath salts" abuse.

 描述（由申请人提供）：过去 5 年，合成卡西酮（例如 MDPV 和甲基酮）的滥用急剧增加，这些药物以“浴盐”的形式销售，并且可以在互联网和市场上广泛购买。当地商店认为“浴盐”是“安全”和“合法的兴奋剂”。目前尚不清楚导致这些高滥用率和毒性的机制，但值得注意的是，“浴盐”最常见的是多种精神活性药物的混合物，包括两种不同合成卡西酮的混合物，或合成卡西酮和咖啡因的混合物该提案包含三个独立的目标，重点是比较“浴盐”混合物（MDPV + 甲基酮、MDPV + 咖啡因和甲基酮 + 咖啡因）的增强效果、复发相关行为和毒性作用。该项目将完善的滥用（自我给药）和毒性（心血管记录）动物模型与等辐射分析相结合，以评估常见“浴盐”混合物的高度创新假设（ 1) 比单独的合成卡西酮更有效和更有效的增强剂；(2) 比单独的合成卡西酮更有效地增强涉及复发的药物刺激关联；以及 (3) 更有效地产生作用；心动过速和高血压以及“浴盐”毒理学的其他特征与单独的合成卡西酮相比，所提出的研究结果将提供有关导致“浴盐”滥用和毒性高发生率的因素的重要信息。新的知识将指导针对不断增加和不断演变的“浴盐”滥用问题开发新的和有针对性的治疗方法。