Rahman Shafiqur, Bardo Michael T
Center for Drug Abuse Research Translation, University of Kentucky, BBSRB, Room 447, 741 S. Limestone, Lexington, KY 40536-0509, USA.
Brain Res. 2008 Mar 4;1197:40-6. doi: 10.1016/j.brainres.2007.12.052. Epub 2008 Jan 4.
In addition to dopamine (DA), evidence indicates that glutamatergic regulation of the mesolimbic reward pathway is involved in mediating the abuse-related effects of psychostimulants, including amphetamine. Since rats raised in an enrichment condition (EC) during development are more sensitive to the locomotor stimulant effects of acute amphetamine compared to rats raised in an impoverished condition (IC), the present study examined amphetamine-induced extracellullar glutamate and aspartate levels in the nucleus accumbens (NAcc) of EC and IC rats using in vivo microdialysis coupled with HPLC-electrochemical detection. Basal extracellular levels of glutamate or aspartate were not significantly different between EC and IC rats. Acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) increased extracellular glutamate levels in NAcc of EC rats (137% or 305% of basal) and IC rats (120% or 187% of basal). Similarly, acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) elevated aspartate levels in NAcc of EC rats (148% or 237% of basal) and IC rats (115% or 170% of basal). Glutamate levels were elevated by amphetamine to a greater extent in EC rats than in IC rats. Pretreatment with systemic MK-801 (0.25 mg/kg, ip), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, prevented the acute amphetamine-induced increase in extracellular glutamate and aspartate levels in NAcc. Overall, these results suggest that alterations in glutamate in the NAcc may be involved in the environment-dependent effects of amphetamine.
除多巴胺（DA）外，有证据表明，中脑边缘奖赏通路的谷氨酸能调节参与介导包括苯丙胺在内的精神兴奋剂的滥用相关效应。由于在发育过程中饲养于丰富环境（EC）中的大鼠比饲养于贫乏环境（IC）中的大鼠对急性苯丙胺的运动兴奋作用更敏感，因此本研究使用体内微透析结合高效液相色谱 - 电化学检测法，检测了EC和IC大鼠伏隔核（NAcc）中苯丙胺诱导的细胞外谷氨酸和天冬氨酸水平。EC和IC大鼠之间谷氨酸或天冬氨酸的基础细胞外水平无显著差异。急性全身注射苯丙胺（0.5或2.0 mg/kg，皮下注射）可使EC大鼠NAcc中的细胞外谷氨酸水平升高（分别为基础水平的137%或305%），IC大鼠中也升高（分别为基础水平的120%或187%）。同样，急性全身注射苯丙胺（0.5或2.0 mg/kg，皮下注射）可使EC大鼠NAcc中的天冬氨酸水平升高（分别为基础水平的148%或237%），IC大鼠中也升高（分别为基础水平的115%或170%）。苯丙胺使谷氨酸水平升高的程度在EC大鼠中比在IC大鼠中更大。全身注射非竞争性N - 甲基 - d - 天冬氨酸（NMDA）受体拮抗剂MK - 801（0.25 mg/kg，腹腔注射）预处理可阻止急性苯丙胺诱导的NAcc中细胞外谷氨酸和天冬氨酸水平的升高。总体而言，这些结果表明，NAcc中谷氨酸的改变可能参与了苯丙胺的环境依赖性效应。
