Department of Psychology, Macquarie University, NSW 2109, Sydney, Australia.
Neuroscience. 2012 Mar 29;206:100-14. doi: 10.1016/j.neuroscience.2012.01.004. Epub 2012 Jan 10.
The regional expression of the transcription factors c-Fos and FosB/ΔFosB was examined in rats given acute exposure to intravenous methamphetamine (METH) or repeated intravenous METH self-administration. One group of rats self-administered METH via lever pressing in 2 h sessions every day for 3 weeks and on a final test day received self-administered METH as usual. A second group with the same METH self-administration history received saline infusions on the test day, to induce drug-seeking behavior. Other rats were trained with infusions of intravenous saline that were yoked to the passive delivery of METH in the other two groups. On test day, half of these yoked rats received passive METH infusions for the first time, whereas the others received saline as usual. The results showed that acute METH produced a characteristic signature of Fos expression with elevations in striatal, cortical, and extended amygdala regions. Importantly, rats with a 3-week history of METH self-administration displayed similar regional Fos expression to rats receiving METH for the first time. Rats seeking, but not receiving, METH on the test day had augmented Fos in the lateral hypothalamus, septum, and vertical limb of the diagonal band of Broca, suggesting a primary role for these regions in METH-seeking behavior. Both acute and chronic METH activated orexin-positive cells in the perifornical area of the hypothalamus. FosB/ΔFosB was elevated in the lateral hypothalamus, posterior ventral tegmental area, central amygdala, and dorsal raphe of all the rats with a history of METH self-administration. This occurred regardless of whether they received METH on test day, suggesting presence of the long-lived FosB isoform, ΔFosB. Overall, these results show persistent upregulated regional brain Fos and FosB/ΔFosB expression with chronic METH self-administration and indicate a role for the lateral hypothalamus and lateral septum in METH-seeking behavior.
研究人员检测了急性静脉注射 methamphetamine（METH）或重复静脉 METH 自我给药后，转录因子 c-Fos 和 FosB/ΔFosB 在大鼠中的区域性表达。一组大鼠通过杠杆按压在 2 小时的会议中每天进行 3 周的 METH 自我给药，并在最后一个测试日接受常规的 METH 自我给药。具有相同 METH 自我给药史的第二组在测试日接受盐水输注，以诱导觅药行为。其他大鼠接受静脉内盐水输注训练，这些输注与其他两组中 METH 的被动给药相吻合。在测试日，这些被束缚的大鼠中有一半首次接受被动 METH 输注，而另一半则接受常规的盐水输注。结果表明，急性 METH 产生了特征性的 Fos 表达特征，纹状体、皮质和扩展杏仁核区域升高。重要的是，具有 3 周 METH 自我给药史的大鼠显示出与首次接受 METH 的大鼠相似的区域性 Fos 表达。在测试日寻求但未接受 METH 的大鼠，其外侧下丘脑、隔区和 Broca 垂直肢的对角带中的 Fos 增加，表明这些区域在 METH 觅药行为中起主要作用。急性和慢性 METH 均激活下丘脑peri 穹窿区的食欲素阳性细胞。在所有有 METH 自我给药史的大鼠中，外侧下丘脑、腹侧被盖区后部、中央杏仁核和背侧中缝核中的 FosB/ΔFosB 升高。无论它们在测试日是否接受 METH，这都表明存在长寿命的 FosB 同工型ΔFosB。总体而言，这些结果表明慢性 METH 自我给药后，区域性大脑 Fos 和 FosB/ΔFosB 的表达持续上调，并表明外侧下丘脑和外侧隔区在 METH 觅药行为中的作用。
