Marona-Lewicka D, Rhee G S, Sprague J E, Nichols D E
Department of Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Pharmacol Biochem Behav. 1996 Jan;53(1):99-105. doi: 10.1016/0091-3057(95)00205-7.
The present study was designed to characterize further the rewarding and aversive properties of 3,4-methylenedioxymethamphetamine (MDMA), the alpha-ethyl homologue of MDMA (MBDB), fenfluramine, and the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI) using the conditioned place preference paradigm (CPP). Extracellular dopamine (DA) and its metabolite DOPAC were also measured in the nucleus accumbens after systemic drug administration, using in vivo microdialysis in freely moving rats. MDMA produced a positive dose-dependent effect in the CPP test, which was maximal at doses of 5 and 10 mg/kg. MBDB also induced a positive CPP, with a maximum effect at 10 mg/kg. The conditioning effect of MBDB was more than 2.5-fold weaker compared with MDMA. Fenfluramine evoked place aversion at doses of 4, 6, and 10 mg/kg. This effect of fenfluramine was independent of dose. MMAI at doses of 1.25, 2.5, and 5 mg/kg produced no significant effect on place conditioning. At doses of 10 and 20 mg/kg, MMAI produced an effect similar to fenfluramine: Place aversion was independent of dose. In the microdialysis experiments, MDMA significantly elevated extracellular DA and induced a decrease of DOPAC in the nucleus accumbens. Thus, activation of dopaminergic systems may be responsible for the rewarding properties of MDMA-like drugs. In contrast to the effects seen with MDMA, no difference in extracellular DA or DOPAC was seen after injection of MBDB, fenfluramine, or MMAI, even though MBDB weakly induced a place preference. The mechanism responsible for the development of place aversion by fenfluramine or MMAI is unknown at this time and requires further study.
本研究旨在利用条件性位置偏爱范式（CPP）进一步表征3,4-亚甲基二氧甲基苯丙胺（摇头丸）、摇头丸的α-乙基同系物（MBDB）、芬氟拉明以及选择性5-羟色胺释放剂5-甲氧基-6-甲基-2-氨基茚（MMAI）的奖赏和厌恶特性。在自由活动的大鼠中，通过体内微透析法，在全身给药后还测量了伏隔核中的细胞外多巴胺（DA）及其代谢物3,4-二羟基苯乙酸（DOPAC）。摇头丸在CPP试验中产生了剂量依赖性的阳性效应，在5和10mg/kg剂量时效应最大。MBDB也诱导了阳性CPP，在10mg/kg时效应最大。与摇头丸相比，MBDB的条件化效应弱2.5倍以上。芬氟拉明在4、6和10mg/kg剂量时引起位置厌恶。芬氟拉明的这种效应与剂量无关。1.25、2.5和5mg/kg剂量的MMAI对位置条件化没有显著影响。在10和20mg/kg剂量时，MMAI产生了与芬氟拉明类似的效应：位置厌恶与剂量无关。在微透析实验中，摇头丸显著提高了细胞外DA水平，并导致伏隔核中DOPAC水平降低。因此，多巴胺能系统的激活可能是摇头丸类药物奖赏特性的原因。与摇头丸的效应相反，注射MBDB、芬氟拉明或MMAI后，细胞外DA或DOPAC没有差异，尽管MBDB微弱地诱导了位置偏爱。目前尚不清楚芬氟拉明或MMAI引起位置厌恶的机制，需要进一步研究。
