Brenhouse H C, Stellar J R
Department of Psychology, Northeastern University, 360 Huntington Avenue, 125 NI, Boston, MA 02115-5000, USA.
Neuroscience. 2006 Feb;137(3):773-80. doi: 10.1016/j.neuroscience.2005.09.039. Epub 2005 Dec 5.
Repeated cocaine administration in rats can lead to sensitization as evidenced by an increased locomotor response to a subsequent exposure (challenge) dose of cocaine even after a drug-free period. Expression of the immediate early gene product, c-Fos, differs among distinct subregions of the nucleus accumbens shell. This would suggest that these subregions may be differentially involved in sensitization. The present study quantified c-Fos- and deltaFosB-immunoreactive nuclei in subterritories of the nucleus accumbens in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for five consecutive days). Fourteen days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the nucleus accumbens were processed for tyrosine hydroxylase and either c-Fos or deltaFosB. The number of immunoreactive nuclei was quantified in five subregions of the nucleus accumbens shell: the vertex, arch, cone, intermediate zone and ventrolateral zone, which can be identified by differential histological staining for tyrosine hydroxylase. Repeated cocaine administration resulted in robust sensitization that was associated with more deltaFosB in the vertex, arch, and cone compared with saline-treated controls. As previously reported, c-Fos immunoreactivity was increased in the intermediate zone in cocaine-sensitized rats. deltaFosB was significantly elevated in rats that did not receive a cocaine challenge, attesting to the long half-life of this transcription factor. These results provide further evidence suggesting distinct anatomical neuroadaptations within the nucleus accumbens shell that may play a functional role in psychomotor-stimulant sensitization.
在大鼠中反复给予可卡因会导致敏化，这表现为即使在无药期后，对随后给予的（激发）剂量可卡因的运动反应增强。即刻早期基因产物c-Fos在伏隔核壳的不同亚区域中的表达有所不同。这表明这些亚区域可能在敏化过程中发挥不同的作用。本研究对行为上对可卡因敏感的动物伏隔核亚区域中c-Fos和ΔFosB免疫反应性细胞核进行了定量。大鼠接受诱导敏化的可卡因给药方案（连续五天每天两次腹腔注射15mg/kg）。最后一次注射后14天，给大鼠腹腔注射一次激发剂量的可卡因（15mg/kg），并在2小时后处死。对伏隔核切片进行酪氨酸羟化酶以及c-Fos或ΔFosB处理。在伏隔核壳的五个亚区域中对免疫反应性细胞核的数量进行定量：顶点、弓形、锥形、中间区和腹外侧区，这些区域可通过酪氨酸羟化酶的差异组织学染色来识别。反复给予可卡因导致强烈的敏化，与生理盐水处理的对照组相比，顶点、弓形和锥形区域中的ΔFosB更多。如先前报道，在可卡因致敏大鼠的中间区c-Fos免疫反应性增加。在未接受可卡因激发的大鼠中，ΔFosB显著升高，证明了这种转录因子的长半衰期。这些结果提供了进一步的证据，表明伏隔核壳内存在不同的解剖学神经适应性变化，这些变化可能在精神运动兴奋剂敏化中发挥功能性作用。
