Keys A S, Mark G P, Emre N, Meshul C K
Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland 97201, USA.
Synapse. 1998 Dec;30(4):393-401. doi: 10.1002/(SICI)1098-2396(199812)30:4<393::AID-SYN6>3.0.CO;2-H.
Alterations in the density of GABA and glutamate immunolabeling within nerve terminals in the shell region of the nucleus accumbens were assessed in rats withdrawn from intravenous cocaine exposure. Four groups of rats were used: one group self-administered cocaine (0.42 mg/kg/infusion) in daily 3-h sessions for approximately 2 weeks, two additional groups received either saline or cocaine in a noncontingent fashion, and a fourth comprised a drug-naive, age-matched control group. Immunogold electron microscopy was used to quantify presynaptic terminal GABA and glutamate density within the vesicular and mitochondrial pools approximately 18 days following the last drug or saline exposure in the treatment groups. A significant 27.7% decrease in vesicular glutamate density within asymmetrical nerve terminals was observed in animals that self-administered cocaine as compared to controls. This group also showed an 18.6% decrease in vesicular nerve terminal glutamate immunolabeling as compared to animals that were administered a similar total dose of cocaine in a response-independent fashion. No significant changes in the density of nerve terminal GABA vesicular immunolabeling were observed in any groups. For both transmitters, no differences were detected in the density of immunolabeling within the presynaptic mitochondrial (i.e., metabolic) pool. These results demonstrate that glutamate density is suppressed in the shell region of the nucleus accumbens following withdrawal from 2 weeks of cocaine exposure. The findings also suggest that the motivational aspects that accompany self-administration may participate in this reduction.
在从静脉注射可卡因暴露中撤药的大鼠中，评估了伏隔核壳区神经末梢内GABA和谷氨酸免疫标记密度的变化。使用了四组大鼠：一组大鼠每天进行3小时的可卡因自我给药（0.42毫克/千克/输注），持续约2周；另外两组以非偶然方式接受生理盐水或可卡因；第四组为未接触过药物、年龄匹配的对照组。在治疗组最后一次药物或生理盐水暴露约18天后，使用免疫金电子显微镜对囊泡池和线粒体池内突触前终末的GABA和谷氨酸密度进行定量。与对照组相比，自我给药可卡因的动物不对称神经末梢内囊泡谷氨酸密度显著降低了27.7%。与以非反应依赖方式给予相似总剂量可卡因的动物相比，该组囊泡神经末梢谷氨酸免疫标记也降低了18.6%。在任何组中均未观察到神经末梢GABA囊泡免疫标记密度的显著变化。对于这两种神经递质，突触前线粒体（即代谢）池内免疫标记密度均未检测到差异。这些结果表明，在暴露于可卡因2周后撤药，伏隔核壳区的谷氨酸密度受到抑制。研究结果还表明，自我给药伴随的动机因素可能参与了这种降低。
