Psychopharmacology Laboratory, Center for Neuroscience and Behavior, Department of Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016, USA.
Reichel Neuropsychopharmacology Laboratory, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA.
Pharmacol Biochem Behav. 2022 Oct;220:173470. doi: 10.1016/j.pbb.2022.173470. Epub 2022 Oct 4.
Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA.
Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mg/kg of MDPV or 1 mg/kg of MDMA.
MDPV and MDMA induced taste avoidance in males and females (all p's < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all p's < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all p's < 0.05), but it had no effect on those induced by MDMA (all p's > 0.05).
The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.
在合成卡西酮使用者中，多药使用的情况得到了充分记录，尽管这种使用的后果尚未得到充分描述。在临床前研究中，有报道称，预先暴露于一种药物会减轻其他药物的厌恶效应，这对它们的滥用潜力有影响。本研究的目的是调查预先暴露于合成卡西酮甲酮对 MDPV 和 MDMA 的厌恶效应的影响。
雄性和雌性 Sprague-Dawley 大鼠每隔 4 天接受 10mg/kg 的甲酮（共接受 5 次注射），然后进行 1.8mg/kg 的 MDPV 或 1mg/kg 的 MDMA 的味觉回避训练。
MDPV 和 MDMA 诱导雄性和雌性大鼠产生味觉回避（所有 p 值均<0.05）。在雄性大鼠中，甲酮预先暴露减轻了 MDPV 和 MDMA 诱导的回避（所有 p 值均<0.05），而 MDPV 的减轻作用更大。在雌性大鼠中，甲酮预先暴露减轻了 MDPV 诱导的回避（所有 p 值均<0.05），但对 MDMA 诱导的回避没有影响（所有 p 值均>0.05）。
暴露于甲酮对 MDPV 和 MDMA 诱导的味觉回避的影响取决于药物（MDPV > MDMA）和性别（仅 MDMA 对雄性大鼠）。甲酮预先暴露对 MDPV 和 MDMA 的抑制作用从它们共同的神经化学作用方面进行了讨论。这些发现表明，甲酮使用史可能会降低 MDPV 和 MDMA 的厌恶效应，这可能对涉及合成卡西酮的多药使用有影响。
