Department of Biology, University of Puerto Rico, Río Piedras.
Curr Neuropharmacol. 2011 Mar;9(1):17-20. doi: 10.2174/157015911795017010.
Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaine's locomotion effects in a planarian animal model (Pagán et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg significantly blocked cocaine's inhibitory effect on DA neuronal firing rate and bursting activity (p< 0.05, two way ANOVA). We propose that parthenolide might inhibit cocaine's effects on VTA DA neurons via its interaction with a common binding site at monoamine transporters. It is suggested that parthenolide could have a potential use as an overdose antidote or therapeutic agent to cocaine intoxication.
慢性可卡因给药会导致儿茶酚胺再摄取抑制，从而增强奖励和动机行为。腹侧被盖区多巴胺能（VTA DA）神经元的放电与奖励预测信号的变化有关。急性可卡因注射会抑制脊椎动物中推定的 VTA DA 细胞的放电。小白菊内酯，一种从小白菊（Tanacetum parthenium）植物中分离出的化合物，已被证明可在扁形动物动物模型中显著抑制可卡因的运动效应（Pagan 等人，2008 年）。在这里，我们研究了小白菊内酯对麻醉雄性大鼠（250-300g）中推定的 VTA DA 神经元自发放电活动的影响。在静脉内（i.v.）给予小白菊内酯后，通过静脉内（i.v.）给予 1mg/kg 可卡因注射来分析单细胞记录。结果表明，小白菊内酯在 0.125mg/kg 和 0.250mg/kg 时显著阻断了可卡因对 DA 神经元放电率和爆发活动的抑制作用（p<0.05，双向 ANOVA）。我们提出小白菊内酯可能通过与单胺转运体的共同结合位点相互作用来抑制可卡因对 VTA DA 神经元的作用。建议小白菊内酯可能具有作为过量解毒剂或治疗可卡因中毒的潜在用途。
