Aberg Maria, Wade Dean, Wall Erin, Izenwasser Sari
Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, 1600 NW 10th Avenue, Rm 4113A (D-80), Miami, FL 33136, USA.
Neurotoxicol Teratol. 2007 Jan-Feb;29(1):37-46. doi: 10.1016/j.ntt.2006.09.002. Epub 2006 Sep 14.
MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA.
摇头丸(迷幻药)是青少年常用的一种毒品,许多摇头丸使用者还使用其他非法药物。目前尚不清楚青少年时期使用摇头丸对后续可卡因反应的影响是否与成年人不同。本研究考察了摇头丸对青少年和成年大鼠可卡因条件性奖赏的影响。在这些实验开始时,青少年大鼠处于出生后第33天(PND 33),成年大鼠处于PND 60。每只大鼠用摇头丸(2或5毫克/千克/天)或赋形剂处理7天,并测量其运动活性。五天后开始进行可卡因条件性位置偏爱(CPP)实验。大鼠训练3天,上午注射生理盐水,下午在30分钟的实验时段内注射10毫克/千克可卡因,并在第四天进行测试。摇头丸刺激了两个年龄组的活动,但对成年大鼠的影响更大。成年大鼠对较低剂量摇头丸的运动兴奋作用产生了敏化,两个组对较高剂量的摇头丸均产生了敏化。在赋形剂处理的青少年大鼠中,可卡因未产生CPP,但在摇头丸处理后观察到显著的CPP。相比之下,成年大鼠在使用摇头丸后,可卡因诱导的CPP降低。在两周后的重新测试中,这些影响仍然明显。因此,在目前的条件下,摇头丸增加了青少年对可卡因的条件性奖赏,而降低了成年大鼠对可卡因的条件性奖赏。这些发现表明,在这个关键的发育时期接触摇头丸可能比成年期带来更大的风险,并且男性青少年在使用摇头丸后可能特别容易受到兴奋剂滥用风险的影响。