Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization
Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization
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DOI：
10.1046/j.1471-4159.1999.0722397.x
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发表时间：
1999-06-01
影响因子：
4.7
通讯作者：
Kalivas, PW
中科院分区：
文献类型：
--
作者：
Churchill, L;Swanson, CJ;Kalivas, PW
伏隔核和腹侧被盖区谷氨酸传递的增加被认为是反复服用可卡因致敏行为反应的机制。在停止每日可卡因注射1周后的24小时和3周，通过免疫印迹对大鼠脑核中的谷氨酸受体GluR1、GluR2/3和NMDAR1亚基进行定量。每日第一次和最后一次注射可卡因后监测运动行为，与第一次注射相比，最后一次注射可卡因后运动活动增加约20%的大鼠被认为发生了行为致敏，发生行为致敏的受试者在停药3周时伏隔核GluR1水平显著升高，而在停药24小时时则没有。致敏动物的腹侧被盖区NMDAR1和GluR1水平在戒断后第1天显著增加，但在戒断后第3周没有增加。每天暴露于可卡因的大鼠没有发生行为致敏(
Increased glutamate transmission in the nucleus accumbens and ventral tegmental area has been proposed as a mechanism underlying sensitized behavioral responses to repeated cocaine administration. GluR1, GluR2/3, and NMDAR1 subunits of glutamate receptors were quantified from immunoblots in these brain nuclei in rats at 24 h and 3 weeks after discontinuing 1 week of daily cocaine injections. Motor behavior was monitored after the first and last injections of daily cocaine, and those rats that showed >20% increase in motor activity after the last compared with the first injection were considered to have developed behavioral sensitization, The subjects that developed behavioral sensitization showed a significant increase in GluR1 levels in the nucleus accumbens at 3 weeks but not at 24 h of withdrawal, Conversely, sensitized animals showed a significant increase in NMDAR1 and GluR1 levels in the ventral tegmental area at 1 day but not at 3 weeks of withdrawal, None of these increases occurred in the rats exposed to daily cocaine that did not develop behavioral sensitization (