合成卡西酮在非法药物市场上越来越受欢迎,然而,他们的潜在虐待仍然知之甚少。在这项研究中,斑马鱼被用来比较三种卡西酮类似物的成瘾潜力,即戊酮,eutylone,和N-乙基戊酮(NEP)。斑马鱼通过连续两天每天两次口服管饲法接受各种剂量(0至60mg/kg)的卡西酮类似物,以诱导条件性位置偏爱(CPP)。戊酮,eutylone,和NEP剂量依赖性诱导的CPP,在20mg/kg的剂量下,NEP显示出明显高于戊酮和乙酮的CPP。接受60毫克/千克卡西诺的鱼灭绝了,然后是由药物引发引发的恢复。NEP需要六次会议才能达到灭绝标准,紧随其后的是Eutylone,这需要四次会议,和戊酮,这需要三次会议。此外,剂量为40mg/kg的NEP和Eutylone可以恢复已熄灭的CPP,而60mg/kg的戊酮是CPP恢复所必需的。还在初始恢复后7天和14天评估了恢复易感性的持久性。所有三种卡西酮类似物诱导的CPP可以在初始恢复后7天恢复,而只有NEP诱导的CPP,但不是戊酮和eutylone,可以在14天后恢复。考虑到诱导CPP的效力,抵抗灭绝,以及复职的倾向,卡西酮类似物的滥用责任等级顺序可能如下:NEP>戊酮>戊酮。这些发现表明,斑马鱼CPP范式可以作为评估物质相对滥用责任的可行模型。
Synthetic cathinones have gained increasing popularity in the illicit drug market, yet their abuse potential remains poorly understood. In this study, zebrafish were used to compare the addictive potential of three cathinone analogs, namely pentylone, eutylone, and N-ethylpentylone (NEP). The zebrafish received various doses (0 to 60 mg/kg) of the cathinone analogs by oral gavage over two sessions per day for two consecutive days to induce conditioned place preference (CPP). Pentylone, eutylone, and NEP dose-dependently induced CPP, with NEP showing significantly higher CPP than pentylone and eutylone at the dose of 20 mg/kg. The fish that received 60 mg/kg of cathinones underwent extinction, followed by
reinstatement triggered by drug priming. NEP required six sessions to meet the criteria of extinction, followed by eutylone, which required four sessions, and pentylone, which required three sessions. Furthermore, NEP and eutylone at a dose of 40 mg/kg could reinstate the extinguished CPP, while 60 mg/kg of pentylone was necessary for CPP
reinstatement. The persistence of susceptibility to
reinstatement was also assessed at 7 and 14 days after the initial
reinstatement. The CPP induced by all three cathinone analogs could be reinstated 7 days after the initial
reinstatement, whereas only CPP induced by NEP, but not pentylone and eutylone, could be reinstated again after 14 days. Considering the potency to induce CPP, resistance to extinction, and the propensity for
reinstatement, the abuse liability rank order of the cathinone analogs might be as follows: NEP > eutylone > pentylone. These findings suggest that the zebrafish CPP paradigm can serve as a viable model for assessing the relative abuse liability of substances.