Bath salts: abuse-related and toxic effects

 描述（由申请人提供）：在过去的5年中，合成卡西酮的滥用急剧增加（例如，MDPV和甲酮），这是作为“浴盐”销售，并广泛购买在互联网上和当地商店作为“安全”和“法律的高点。除了滥用的可能性很高之外，“浴盐”也有很高的潜在毒性，其特征是严重的心血管和神经精神并发症。虽然目前尚不清楚造成这些高滥用率和毒性的机制，但必须指出，“浴盐”通常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。该提案由三个独立的目标组成，重点是比较“浴盐”混合物（MDPV +甲酮，MDPV +咖啡因和甲酮+咖啡因）与单独合成卡西酮（MDPV和甲酮）的强化效果，复发相关行为和毒性作用。这个项目结合了成熟的虐待动物模型（自我给药）和毒性（心血管记录）与等效线分析，以评估高度创新的假设，即常见的“浴盐”混合物（1）比单独合成卡西酮更有效和更有效;（2）比单独合成卡西酮更有效地加强与复发有关的药物刺激关联;和（3）在产生心动过速和高血压以及“浴盐”毒性组的其它特征方面比单独的合成卡西酮更强效和有效。总之，拟议研究的结果将提供有关导致“浴盐”滥用率高和毒性高的因素的基本信息。这一新知识将指导开发新的和有针对性的治疗方法，以解决不断增加和不断发展的“浴盐”滥用问题。

 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.