Wang J Q, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.
Brain Res. 1995 Mar 6;673(2):262-74. doi: 10.1016/0006-8993(94)01422-e.
Quantitative in situ hybridization histochemistry was used to compare the effects of AMPH administration on mRNAs coding for zif/268, a member of the zinc finger family of immediate early genes, and the opioid peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in rat striatum after 3 dosing schedules: (1) acute; (2) once a day for 5 days, and (3) once a day for 5 days followed 10 days later by a challenge dose. Behavioral ratings indicated that the activity of rats was significantly higher after 5 daily AMPH (5 mg/kg, i.p.) injections than after a single 5 mg/kg injection and that the activity of AMPH-pretreated rats was significantly higher than that of saline-pretreated rats after a 1 mg/kg challenge dose 10 days later. Three hours after acute administration of AMPH to naive rats, PPD mRNA expression in the dorsal (caudatoputamen) and ventral (nucleus accumbens, NAc) striatum as well as PPE and zif/268 mRNA expression in the dorsal, but not ventral, striatum were increased as compared to saline-treated rats. Five daily treatments with AMPH augmented acute AMPH-induced increases in PPD mRNA expression in the caudatoputamen but not in the NAc. The increase in striatal zif/268 mRNA expression induced by acute AMPH was, in contrast, reduced after 5 daily treatments with AMPH. AMPH induced PPE expression to the same extent in rats treated with one or 5 daily injections. Hybridization performed 3 h after AMPH challenge in AMPH-pretreated rats failed to demonstrate augmentation of AMPH-stimulated zif/268, PPD, or PPE mRNA expression in the striatum as compared to saline-pretreated rats. These results indicate that an augmented response of PPD and a decreased response of zif/268 mRNA expression in striatal neurons are closely associated with the initiation of behavioral sensitization induced by repeated, intermittent AMPH treatments. In contrast, a clear dissociation exists between the expression of sensitized behaviors and unsensitized zif/268, PPD and PPE mRNA in the striatum in response to a challenge dose of AMPH. Possible functional implications of these alterations in the initiation and expression of AMPH-induced behavioral sensitization are discussed.
采用定量原位杂交组织化学技术，比较了安非他明（AMPH）给药后，在3种给药方案下，对大鼠纹状体中编码zif/268（锌指家族即刻早期基因成员之一）、阿片肽前强啡肽原（PPD）和前脑啡肽原（PPE）的mRNA的影响：（1）急性给药；（2）每天1次，连续5天；（3）每天1次，连续5天，10天后给予一次激发剂量。行为评分表明，每天注射5次AMPH（5mg/kg，腹腔注射）后大鼠的活动明显高于单次注射5mg/kg后，且10天后给予1mg/kg激发剂量后，AMPH预处理大鼠的活动明显高于生理盐水预处理大鼠。给未处理的大鼠急性注射AMPH 3小时后，与生理盐水处理的大鼠相比，背侧（尾壳核）和腹侧（伏隔核，NAc）纹状体中PPD mRNA表达以及背侧纹状体中PPE和zif/268 mRNA表达增加，但腹侧纹状体中未增加。每天用AMPH处理5次增强了急性AMPH诱导的尾壳核中PPD mRNA表达的增加，但NAc中未增加。相反，每天用AMPH处理5次后，急性AMPH诱导的纹状体中zif/268 mRNA表达的增加减少。AMPH对单次或每天注射5次的大鼠诱导PPE表达的程度相同。与生理盐水预处理的大鼠相比，在AMPH预处理的大鼠中，AMPH激发后3小时进行的杂交未能显示纹状体中AMPH刺激的zif/268、PPD或PPE mRNA表达增强。这些结果表明，纹状体神经元中PPD反应增强和zif/268 mRNA表达反应降低与重复、间歇性AMPH处理诱导的行为敏化的起始密切相关。相反，在对AMPH激发剂量的反应中，纹状体中敏化行为的表达与未敏化的zif/268、PPD和PPE mRNA之间存在明显的分离。讨论了这些变化在AMPH诱导的行为敏化起始和表达中的可能功能意义。
