Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
Psychopharmacology (Berl). 2019 Mar;236(3):925-938. doi: 10.1007/s00213-018-5052-z. Epub 2018 Oct 4.
MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present in bath salts. It is a powerful psychostimulant and blocker of the dopamine transporter (DAT), like cocaine. It is known that acute exposure to psychostimulants induces rapid changes in DAT function.
To investigate the effects of MDPV on DAT function comparing with cocaine.
Binding of [H]WIN 35428 was performed on PC 12 cells treated with MDPV and washed. Rat striatal synaptosomes were incubated with MDPV or cocaine (1 μM) for 1 h and [H]dopamine (DA) uptake was performed. Also, different treatments with MDPV or cocaine were performed in Sprague-Dawley rats to assess locomotor activity and ex vivo [H]DA uptake.
MDPV increased surface [H]WIN 35428 binding on PC 12 cells. In vitro incubation of synaptosomes with MDPV produced significant increases in V and K for [H]DA uptake. In synaptosomes from MDPV- (1.5 mg/kg, s.c.) and cocaine- (30 mg/kg, i.p.) treated rats, there was a significantly higher and more persistent increase in [H]DA uptake in the case of MDPV than cocaine. Repeated doses of MDPV developed tolerance to this DAT upregulation and 24 h after the 5-day treatment with MDPV, [H]DA uptake was reduced. However, a challenge with the same drugs after withdrawal recovered the DAT upregulation by both drugs and showed an increased response to MDPV vs the first dose. At the same time, animals were sensitized to the stereotypies induced by both psychostimulants.
MDPV induces a rapid and reversible functional upregulation of DAT more powerfully and lasting than cocaine.
MPVP（3,4-亚甲二氧基吡咯戊酮）是一种存在于浴盐中的合成苯丙胺类兴奋剂。它是一种强大的精神兴奋剂和多巴胺转运体（DAT）阻断剂，与可卡因类似。已知急性暴露于精神兴奋剂会导致 DAT 功能的快速变化。
研究 MDPV 对 DAT 功能的影响，并与可卡因进行比较。
用 MDPV 处理并洗涤后的 PC12 细胞进行 [H]WIN 35428 结合实验。将大鼠纹状体突触小体与 MDPV 或可卡因（1μM）孵育 1 小时，进行 [H]多巴胺（DA）摄取实验。此外，还在 Sprague-Dawley 大鼠中进行不同的 MDPV 或可卡因处理，以评估运动活性和离体 [H]DA 摄取。
MDPV 增加了 PC12 细胞表面 [H]WIN 35428 结合。在体外孵育的突触小体中，MDPV 使 [H]DA 摄取的 V 和 K 显著增加。在 MDPV（1.5mg/kg，sc）和可卡因（30mg/kg，ip）处理的大鼠的突触小体中，MDPV 引起的 [H]DA 摄取增加更为显著和持久，而可卡因则没有。重复给予 MDPV 会导致对这种 DAT 上调的耐受性，并且在 MDPV 治疗 5 天后的 24 小时，[H]DA 摄取减少。然而，在停药后用相同的药物进行挑战，恢复了两种药物的 DAT 上调，并显示出对 MDPV 的反应增加，与第一剂量相比。同时，动物对两种精神兴奋剂引起的刻板行为产生了敏感性。
MDPV 诱导 DAT 的快速和可逆功能上调比可卡因更有力和持久。
