Ball Kevin T, Budreau Daniel, Rebec George V
Department of Psychology and Program in Neural Science, Psychology Building, Indiana University, 1101 East 10th Street, Bloomington, IN 47405-7007, USA.
Brain Res. 2003 Dec 24;994(2):203-15. doi: 10.1016/j.brainres.2003.09.037.
3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused amphetamine derivative that increases dopamine (DA) and serotonin release via a reverse transport mechanism. Changes in the activity of striatal neurons in response to increased DA transmission may shape the behavioral patterns associated with amphetamine-like stimulants. To determine how the striatum participates in MDMA-induced locomotor activation, we recorded the activity of >100 single units in the striatum of freely moving rats in response to a dose that increased motor activation (5.0 mg/kg). MDMA had a predominantly excitatory effect on neuronal activity that was positively correlated with the magnitude of locomotor activation. Categorizing neurons according to baseline locomotor responsiveness revealed that MDMA excited significantly more neurons showing movement-related increases in activity compared to units that were non-movement-related or associated with movement-related decreases in activity. Further analysis revealed that the drug-induced striatal activation was not simply secondary to the behavioral change, indicating a primary action of MDMA on striatal motor circuits. Prior administration of SCH-23390 (0.2 mg/kg), a D(1) antagonist, resulted in a late onset of MDMA-induced locomotion, which correlated positively with delayed neuronal excitations. Conversely, prior administration of eticlopride (0.2 mg/kg), a D(2) antagonist, completely abolished MDMA-induced locomotion, which paralleled its blockade of MDMA-induced excitatory neuronal responses. Our results highlight the importance of striatal neuronal activity in shaping the behavioral response to MDMA, and suggest that DA D(1) and D(2) receptors have distinct functional roles in the expression of MDMA-induced striatal and locomotor activation.
3,4-亚甲基二氧甲基苯丙胺（摇头丸）是一种被广泛滥用的苯丙胺衍生物，它通过逆向转运机制增加多巴胺（DA）和5-羟色胺的释放。纹状体神经元活动的变化对多巴胺传递增加的反应，可能会形成与苯丙胺类兴奋剂相关的行为模式。为了确定纹状体如何参与摇头丸诱导的运动激活，我们记录了自由活动大鼠纹状体中100多个单个神经元的活动，以响应增加运动激活的剂量（5.0毫克/千克）。摇头丸对神经元活动主要有兴奋作用，这与运动激活的程度呈正相关。根据基线运动反应性对神经元进行分类显示，与非运动相关或与运动相关活动减少的神经元相比，摇头丸能显著兴奋更多显示与运动相关活动增加的神经元。进一步分析表明，药物诱导的纹状体激活并非仅仅是行为变化的继发结果，这表明摇头丸对纹状体运动回路有主要作用。预先给予D(1)拮抗剂SCH-23390（0.2毫克/千克）会导致摇头丸诱导的运动延迟出现，这与延迟的神经元兴奋呈正相关。相反，预先给予D(2)拮抗剂依替必利（0.2毫克/千克）则完全消除了摇头丸诱导的运动，这与其对摇头丸诱导的兴奋性神经元反应的阻断作用平行。我们的结果突出了纹状体神经元活动在塑造对摇头丸行为反应中的重要性，并表明多巴胺D(1)和D(2)受体在摇头丸诱导的纹状体和运动激活表达中具有不同的功能作用。
