Betancur C, Rostène W, Bérod A
INSERM U339, Hôpital Saint-Antoine, Paris, France.
Brain Res Mol Brain Res. 1997 Mar;44(2):334-40. doi: 10.1016/s0169-328x(96)00289-6.
The effects of chronic cocaine administration on neurotensin (NT) mRNA expression were investigated in the rat brain using in situ hybridization. Adult Wistar rats were injected daily with cocaine (15 mg/kg i.p.) or saline for 10 days. One hour after the last injection, the brains were removed and coronal sections of the nucleus accumbens and striatum processed for in situ hybridization using a 35S-labeled NT mRNA oligonucleotide probe. Repeated administration of cocaine induced a specific increase in the expression of NT mRNA in the shell of the nucleus accumbens whereas no changes were observed in the core compartment. In addition, cocaine enhanced the expression of the NT gene in neurons confined to the posterior dorsomedial striatum, but did not alter this same region in the anterior striatum. A strong increase in NT mRNA expression was also observed in rats treated with cocaine in the ventrolateral region of the striatum, the fundus striati. No modifications were seen in the dorsolateral or ventromedial striatum, the lateral septum, or the olfactory tubercle. These findings demonstrate that cocaine affects NT mRNA expression in discrete populations of neurons confined to the shell of the nucleus accumbens and dorsomedial and ventrolateral striatum of the rat. The shell of the nucleus accumbens is a limbic area considered the locus of the reinforcing and locomotor activating properties of cocaine while the dorsal striatum is implicated in the regulation of motor output, and appears to be involved in the stereotypies induced by cocaine. The specific increases in NT gene expression induced by chronic cocaine suggest that these changes could be physiologically relevant for the behavioral effects of psychostimulant drugs.
采用原位杂交技术，研究了长期给予可卡因对大鼠脑内神经降压素（NT）mRNA表达的影响。成年Wistar大鼠每天腹腔注射可卡因（15mg/kg）或生理盐水，持续10天。末次注射1小时后，取出大脑，对伏隔核和纹状体进行冠状切片，使用35S标记的NT mRNA寡核苷酸探针进行原位杂交处理。重复给予可卡因可导致伏隔核壳部NT mRNA表达特异性增加，而核心区未观察到变化。此外，可卡因增强了局限于背内侧纹状体后部神经元中NT基因的表达，但未改变前纹状体同一区域的表达。在接受可卡因治疗的大鼠纹状体腹外侧区（纹状体底部）也观察到NT mRNA表达显著增加。在背外侧或腹内侧纹状体、外侧隔或嗅结节中未见改变。这些发现表明，可卡因影响大鼠伏隔核壳部以及背内侧和腹外侧纹状体中离散神经元群体的NT mRNA表达。伏隔核壳部是一个边缘区域，被认为是可卡因强化和运动激活特性的位点，而背侧纹状体与运动输出的调节有关，似乎也参与了可卡因诱导的刻板行为。长期给予可卡因诱导的NT基因表达特异性增加表明，这些变化可能在生理上与精神兴奋药物的行为效应相关。
