Seaman Robert W, Lamon Kariann, Whitton Nicholas, Latimer Brian, Sulima Agnieszka, Rice Kenner C, Murnane Kevin S, Collins Gregory T
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA.
Brain Sci. 2024 Mar 6;14(3):258. doi: 10.3390/brainsci14030258.
Recent data suggest that 3,4-methylenedioxypyrovalerone (MDPV) has neurotoxic effects; however, the cognitive and neurochemical consequences of MDPV self-administration remain largely unexplored. Furthermore, despite the fact that drug preparations that contain MDPV often also contain caffeine, little is known regarding the toxic effects produced by the co-use of these two stimulants. The current study investigated the degree to which self-administered MDPV or a mixture of MDPV+caffeine can produce deficits in recognition memory and alter neurochemistry relative to prototypical stimulants. Male Sprague Dawley rats were provided 90 min or 12 h access to MDPV, MDPV+caffeine, methamphetamine, cocaine, or saline for 6 weeks. Novel object recognition (NOR) memory was evaluated prior to any drug self-administration history and 3 weeks after the final self-administration session. Rats that had 12 h access to methamphetamine and those that had 90 min or 12 h access to MDPV+caffeine exhibited significant deficits in NOR, whereas no significant deficits were observed in rats that self-administered cocaine or MDPV. Striatal monoamine levels were not systematically affected. These data demonstrate synergism between MDPV and caffeine with regard to producing recognition memory deficits, highlighting the importance of recapitulating the manner in which drugs are used (e.g., in mixtures containing multiple stimulants, binge-like patterns of intake).
近期数据表明,3,4-亚甲基二氧吡咯戊酮(MDPV)具有神经毒性作用;然而,MDPV自我给药的认知和神经化学后果在很大程度上仍未得到探索。此外,尽管含有MDPV的药物制剂通常也含有咖啡因,但对于这两种兴奋剂共同使用所产生的毒性作用却知之甚少。当前研究调查了自我给药的MDPV或MDPV与咖啡因的混合物相对于典型兴奋剂而言,在多大程度上会导致识别记忆缺陷并改变神经化学。给雄性斯普拉格-道利大鼠提供90分钟或12小时的时间来获取MDPV、MDPV + 咖啡因、甲基苯丙胺、可卡因或生理盐水,持续6周。在任何药物自我给药历史之前以及最后一次自我给药 sessions 后3周,评估新物体识别(NOR)记忆。有12小时获取甲基苯丙胺机会的大鼠以及有90分钟或12小时获取MDPV + 咖啡因机会的大鼠在NOR中表现出显著缺陷,而自我给药可卡因或MDPV的大鼠未观察到显著缺陷。纹状体单胺水平未受到系统性影响。这些数据证明了MDPV和咖啡因在产生识别记忆缺陷方面的协同作用,突出了重现药物使用方式(例如,在含有多种兴奋剂的混合物中,暴饮暴食样的摄入模式)的重要性。