Wu Wei-Ran, Li Na, Sorg Barbara A
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman, WA 99164-6520, USA.
Brain Res. 2003 Nov 21;991(1-2):232-9. doi: 10.1016/j.brainres.2003.03.001.
The present study examined the effects of seven daily saline (1 ml/kg, i.p.) or cocaine injections (15 mg/kg, i.p.) on extracellular dopamine levels in the medial prefrontal cortex (mPFC) after challenge with cocaine or stressful predatory odor presentation given 1 week (early withdrawal) or 3 weeks later (late withdrawal). Cocaine challenge at early withdrawal produced an increase in dopamine levels that was temporally shifted so that maximal levels of dopamine were significantly higher and attained 20 min earlier in the cocaine-pretreated group (maximal levels of saline controls=378% increase, cocaine=494% increase above baseline). Cocaine challenge at late withdrawal produced a similar effect on the temporal shift of maximal dopamine levels, with a significantly higher maximal percent increase of dopamine in cocaine-pretreated rats (saline-pretreated=420% increase, cocaine-pretreated=515% increase). Challenge with TMT, a predatory odor from fox that produces a stress response in rats, produced a maximal 75-200% increase in basal dopamine levels in both groups at both early and late withdrawal times. As with cocaine challenge, daily cocaine produced a leftward shift in the time at which maximal dopamine levels were attained in response to TMT. Cocaine-pretreated animals demonstrated maximal dopamine levels 40-80 min after TMT removal, while saline-pretreated rats showed maximal levels 100-140 min after TMT removal. These results suggest that there are long-term changes in the mPFC dopamine response to subsequent challenge with cocaine as well as a stressful predatory odor. The altered response of mPFC dopamine after repeated daily cocaine may impact relapse to drug-seeking or drug-taking behavior.
本研究检测了连续7天每天腹腔注射生理盐水（1毫升/千克）或可卡因（15毫克/千克），在1周后（早期戒断）或3周后（晚期戒断）给予可卡因激发或应激性捕食者气味刺激后，内侧前额叶皮质（mPFC）细胞外多巴胺水平的变化。早期戒断时给予可卡因激发，可使多巴胺水平升高，且时间上有所偏移，使得可卡因预处理组多巴胺的最高水平显著更高，且比基线水平升高了494%，而生理盐水对照组最高水平仅升高了378%，并提前20分钟达到峰值。晚期戒断时给予可卡因激发，对多巴胺最高水平的时间偏移产生了类似影响，可卡因预处理大鼠多巴胺的最大升高百分比显著更高（生理盐水预处理组升高420%，可卡因预处理组升高515%）。用TMT（一种来自狐狸的捕食者气味，可在大鼠中引发应激反应）进行刺激，在早期和晚期戒断时，两组的基础多巴胺水平最高可升高75% - 200%。与可卡因激发一样，每日注射可卡因使对TMT反应达到多巴胺最高水平的时间向左偏移。可卡因预处理动物在TMT去除后40 - 80分钟出现多巴胺最高水平，而生理盐水预处理大鼠在TMT去除后100 - 140分钟出现最高水平。这些结果表明，mPFC中多巴胺对后续可卡因激发以及应激性捕食者气味的反应存在长期变化。每日重复注射可卡因后mPFC多巴胺反应的改变可能会影响觅药或复吸行为。
