Morley Kirsten C, Cornish Jennifer L, Li Kong M, McGregor Iain S
School of Psychology, University of Sydney, NSW 2006, Australia.
Pharmacol Biochem Behav. 2004 Oct;79(2):331-42. doi: 10.1016/j.pbb.2004.08.004.
The current experiment investigated the effect of 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') preexposure on the acquisition of intravenous amphetamine self-administration and the reinstatement of amphetamine-seeking behavior by either MDMA or amphetamine. Rats were preexposed to a 5-HT depleting regime of MDMA (5 mg/kg every hour for 4 h on two consecutive days) or equivalent vehicle injections. Intravenous self-administration of low dose d-amphetamine (0.03 mg/kg/infusion) on a FR1 schedule was subsequently assessed. The rats were then given 2 weeks of extinction and tested for drug-seeking behavior with priming doses of amphetamine or MDMA. Brains were analysed for monoamine content using high-performance liquid chromatography (HPLC). MDMA-preexposed rats were initially slower to acquire amphetamine self-administration. However, by day 6 of acquisition, there was no difference from controls. Following extinction, amphetamine (1 mg/kg, i.p.) reinstated drug seeking and produced locomotor hyperactivity in both MDMA- and vehicle-pretreated animals. However, MDMA (5 mg/kg, i.p.) was only effective in producing amphetamine seeking and hyperactivity in MDMA-pretreated rats. MDMA pretreatment caused significant decreases in 5-hydroxy-indolacetic acid (5-HIAA) and 5-HT in several brain regions. These results suggest that 5-HT depletion induced by MDMA may initially slow the acquisition of amphetamine self-administration but that MDMA preexposure may also sensitize animals to the locomotor stimulating and priming effects of MDMA on drug-seeking behavior.
当前实验研究了3,4-亚甲基二氧甲基苯丙胺（摇头丸）预先暴露对静脉注射苯丙胺自我给药习得的影响，以及摇头丸或苯丙胺对苯丙胺觅药行为恢复的影响。将大鼠预先暴露于使5-羟色胺耗竭的摇头丸给药方案（连续两天，每小时5毫克/千克，共4小时）或等效的赋形剂注射。随后评估大鼠在固定比率为1的条件下静脉自我注射低剂量右旋苯丙胺（0.03毫克/千克/次注射）的情况。然后让大鼠进行2周的消退训练，并用苯丙胺或摇头丸的激发剂量测试其觅药行为。使用高效液相色谱法（HPLC）分析大脑中的单胺含量。预先暴露于摇头丸的大鼠最初在习得苯丙胺自我给药方面较慢。然而，到习得的第6天，与对照组没有差异。消退训练后，苯丙胺（1毫克/千克，腹腔注射）在预先用摇头丸和赋形剂处理的动物中均恢复了觅药行为并产生了运动性多动。然而，摇头丸（5毫克/千克，腹腔注射）仅在预先用摇头丸处理的大鼠中有效诱导苯丙胺觅药行为和多动。摇头丸预处理导致几个脑区的5-羟吲哚乙酸（5-HIAA）和5-羟色胺显著减少。这些结果表明，摇头丸诱导的5-羟色胺耗竭可能最初会减缓苯丙胺自我给药的习得，但预先暴露于摇头丸也可能使动物对摇头丸对觅药行为的运动刺激和激发作用敏感。
