伏隔核毁损对MAP模型大鼠行为及脑内DA受体的影响

目的 探讨立体定向伏隔核毁损对甲基苯丙胺（MAP）模型大鼠行为学及不同脑区多巴胺D2受体表达的影响。方法 将80只SD大鼠随机分为对照组、模型组、假手术组和手术组，每组各20只。经腹腔注射MAP制备精神分裂症模型，采用立体定向一直流电毁损伏隔核，观察大鼠刻板行为变化；并采用原位杂交法观察额叶、颞叶、边缘区及脑干部位的D2受体表达。结果 与对照组比较，模型组及假手术组大鼠刻板行为评分及各个脑区D2受体表达均显著性增加；与模型组及假手术组比较，手术组大鼠刻板行为评分及各脑区DA受体阳性细胞数目均显著性减少。结论 伏隔核毁损可能通过抑制MAP诱发的脑内D2表达亢进而改变其行为学异常。     

基底外侧杏仁核和隔内侧核毁损对精神分裂症大鼠行为学及中脑D2受体的影响

目的 探讨立体定向基底外侧杏仁核(BLN)和隔内侧核(MS)的联合毁损对甲基苯丙胺(MAP)大鼠中脑脑区多巴胺D2受体(D2DR)表达的影响.方法 48只SD大鼠随机分为对照组、模型组、假手术组、基底外侧杏仁核毁损组(BLN组)、隔内侧核毁损组(MS组)、基底外侧杏仁核与隔内侧核联合毁损组(BLN MS组),每组各8只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向--直流电毁损BLN和MS,原位杂交法观察中脑脑区D2DR的表达.结果 与对照组比较,模型组及假手术组大鼠中脑D2DR表达有非常显著性差异(P<0.01); BLN组、MS组及(BLN MS)组中脑D2DR阳性细胞数目与显著低于模型组(P<0.01).结论 BLN和MS的联合毁损可以抑制使用MAP而诱发的中脑D2DR表达的亢进.     

杏仁核毁损对甲基苯丙胺精神分裂症大鼠边缘区多巴胺D2受体的影响

目的探讨立体定向杏仁核毁损对甲基苯丙胺(methamphetamine,MAP)精神分裂症大鼠脑内边缘区多巴胺D2受体表达的影响.方法40只SD大鼠随机分为对照组、模型组、假手术组和手术组,每组各10只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损杏仁核,原位杂交法观察边缘区多巴胺D2受体的表达.结果与对照组比较,模型组及假手术组大鼠边缘区多巴胺D2受体表达有非常显著性差异(P＜0.01);手术组大鼠边缘区多巴胺DA受体阳性细胞数目与对照组比较差异无显著性(P＜0.01).结论杏仁核毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进.     

杏仁核毁损对甲基苯丙胺大鼠脑内5-HT2A受体的影响

目的探讨杏仁核毁损对甲基苯丙胺（MAP）大鼠脑内5-HT2A受体表达的影响。方法24只SD大鼠分为对照组、模型组、假手术组和手术组，每组各6只；采用腹腔注射MAP制备精神分裂症模型，立体定向毁损杏仁核，采用Sams-Dodd法评定各组动物刻板行为的变化，以PCR技术测定脑组织中5-HT2A受体mRNA的表达。结果杏仁核毁损可明显降低MAP大鼠刻板行为评分（P〈0．05）。各组大鼠额叶、颞叶皮质和中脑均有5-HT2A受体mNRA（61lbp）的阳性表达，且均以额叶皮质表达最为强烈；模型组及假手术组大鼠中脑5-HT2A受体mRNA受体表达的水平明显低于对照组和手术组（P〈0．05）。结论杏仁核毁损可改善MAP大鼠的刻板行为，这可能是通过中脑5-HT2A受体mRNA表达的增高而起作用。     

中隔核毁损对甲基苯丙胺大鼠颞叶皮质多巴胺受体的影响

目的　探讨立体定向中隔核毁损对甲基苯丙胺 (MAP)大鼠脑颞叶皮质多巴胺D2 受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP +毁损组和MAP +假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损中隔核 ,免疫组织化学ABC法观察颞叶皮质D2 受体的表达。结果　与对照组比较 ,MAP组及MAP +假毁损组大鼠颞叶皮质D2 受体表达有非常显著性差异 (P <0 .0 1) ;MAP+毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性 (P >0 .0 5 )。结论　中隔核毁损可以抑制使用MAP而诱发的颞叶皮质D2 表达的亢进。     

杏仁核和扣带回毁损对甲基苯丙胺大鼠边缘区多巴胺受体的影响

目的　探讨立体定向杏仁核和扣带回的联合毁损对甲基苯丙胺 (MAP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP加毁损组和MAP加假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损杏仁核和扣带回 ,免疫组织化学ABC法观察边缘区D2受体的表达。结果　与对照组比较 ,MAP组及MAP加假毁损组大鼠边缘区D2受体表达有非常显著性差异(P <0 0 1) ;MAP加毁损组大鼠边缘区D2受体阳性细胞数目与对照组比较无显著性差异 (P <0 0 1)。结论　杏仁核和扣带回的联合毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进。     

隔核毁损对甲基苯丙胺模型大鼠行为和学习记忆能力的影响

目的观察隔核毁损对甲基苯丙胺（MAP）模型大鼠行为、学习记忆能力的影响。方法先将90只SD大鼠单纯随机分为3组：对照组，MAP组，MAP＋隔核毁损组，每组30只。大鼠腹腔内注射MAP制造精神分裂症动物模型，采用立体定位仪电极毁损隔核，进行刻板行为评分。对照组及MAP＋隔核毁损组进入水迷宫实验；另60只SD大鼠在游泳训练后也进行水迷宫实验，随机分为训练组（无毁损）及训练组（毁损后），每组30只。通过实验检测大鼠的空间学习记忆能力。结果与MAP组比较，MAP＋隔核毁损组大鼠刻板行为评分显著下降。MAP＋隔核毁损组大鼠社会行为良好。水迷宫实验中，MAP＋隔核毁损组在初期空间记忆能力存在缺陷。结论隔核毁损能够实现对大鼠精神分裂症阳性症状的改善，对大鼠初期学习记忆能力及空间定位能力有影响，对已获得的记忆影响不大。     

扣带回毁损对甲基苯丙胺大鼠颞叶皮质多巴胺D2受体的影响

目的探讨扣带回立体定向毁损对甲基苯丙胺(MAP)大鼠脑内颞叶皮质多巴胺D2受体表达的影响.方法80只SD大鼠随机分为对照组、MAP组、MAP 毁损组和MAP 假毁损组,每组各20只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损扣带回,免疫组织化学ABC法观察颞叶皮质D2受体的表达.结果与对照组比较,MAP组及MAP 假毁损组大鼠颞叶皮质D2受体表达差异有显著性(P＜0.01);MAP 毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性(P＞0.05).结论扣带回毁损可以抑制使用MAP而诱发的颢叶皮质D2表达的亢进.     

扣带回毁损对甲基苯丙胺大鼠颞叶皮质多巴胺D2受体的影响

目的探讨扣带回立体定向毁损对甲基苯丙胺(MAP)大鼠脑内颞叶皮质多巴胺D2受体表达的影响。方法80只SD大鼠随机分为对照组、MAP组、MAP 毁损组和MAP 假毁损组,每组各20只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损扣带回,免疫组织化学ABC法观察颞叶皮质D2受体的表达。结果与对照组比较,MAP组及MAP 假毁损组大鼠颞叶皮质D2受体表达差异有显著性(P<0.01);MAP 毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性(P>0.05)。结论扣带回毁损可以抑制使用MAP而诱发的颞叶皮质D2表达的亢进。     

杏仁核毁损对甲基苯丙胺大鼠刻板行为和额叶皮质多巴胺的影响

目的　探讨立体定向杏仁核毁损对甲基苯丙胺 (methamphetamine ,MAP)大鼠刻板行为和额叶皮质多巴胺 (dopamine ,DA)含量的影响。方法　立体定向射频毁损杏仁核 ,经腹腔注射MAP观察大鼠行为学改变 ,荧光分光光度法测定额叶皮质DA含量。结果　杏仁核毁损组大鼠较假手术组大鼠刻板行为评分显著降低 ;甲基苯丙胺逆耐受持续时间显著缩短 ,潜伏期显著延长。MAP大鼠额叶皮质DA含量显著高于对照组 ;杏仁核毁损组的MAP大鼠额叶皮质DA含量显著低于假毁损组。结论　杏仁核毁损可有效地对抗使用甲基苯丙胺而出现的逆耐受现象 ,对额叶皮质DA增高有明显阻断作用     

伏核毁损对精神分裂症模型大鼠行为和学习记忆能力的影响

目的　探讨毁损伏核对调控精神分裂症行为的有效作用及对学习记忆能力的影响 ,为精神分裂症外科治疗提供参考。方法　给大鼠腹腔内注射苯环己哌啶 (PCP)制作精神分裂症动物模型。采用立体定位仪 ,电极毁损大鼠伏核 ,观察社会行为、刻板行为评分 ,并进行Morris水迷宫实验。结果　毁损伏核组能使精神分裂症模型大鼠刻板行为和运动失调有所减轻 ,与假毁损组比较差异具有显著性 (P <0 .0 5 )。水迷宫实验毁损组在初期空间记忆能力的建立上存在缺陷 ,与假毁损组比较差异具有显著性 (P <0 .0 5 )。结论　伏核毁损能改善精神分裂症症状 ,对大鼠初期学习记忆能力有一定影响     

杏仁核和扣带回联合毁损对MAP大鼠脑内多巴胺D2受体的影响

目的探讨联合毁损杏仁核和扣带回对甲基苯丙胺(M AP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法40只SD大鼠随机分为对照组、M AP组、M AP 毁损组和M AP 假毁损组,每组各10只;采用经腹腔注射M AP制备精神分裂症M AP模型,立体定向-射频毁损杏仁核和扣带回,免疫组织化学ABC法观察边缘区D2受体的表达。结果与对照组和M AP 损毁组比较,M AP组及M AP 假毁损组大鼠边缘区D2受体表达有显著性差异(P<0.01);M AP 毁损组大鼠边缘区D2受体阳性细胞率与对照组比较差异无显著性(P>0.05)。结论杏仁核和扣带回的联合毁损可抑制使用M A P诱发的边缘区D2受体表达的亢进。     

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats.

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to D-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5-15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.     

Spreading depression in the cortex differently modulates dopamine release in rat mesolimbic and nigrostriatal terminal fields

The effects of cortical spreading depression (SD) on evoked dopamine release in mesolimbic (nucleus accumbens) and nigrostriatal (nucleus caudatus) terminal fields were studied by in vivo voltammetry in anesthetized rats. Dopamine release was evoked by electrical stimulation of medial forebrain bundle (20 Hz, 100 pulses). Local application of 3 M KCl on the dura initiated SD in the cortex. It was found that SD modulated evoked dopamine release in subcortical structures at the same time when the wave of depression of cortical activity reached reciprocally connected subcortical areas. This cortical depression increased stimulated dopamine release in the nucleus accumbens and decreased dopamine release in the nucleus caudatus. In agreement with these results, electrical stimulation of the prefrontal cortex at 20 Hz, synchronized with medial forebrain bundle stimulation, decreased evoked dopamine release in the nucleus accumbens. Areas of the cortex which modulated dopamine release in these two terminal fields were spatially separated by at least 5 mm from each other. It is proposed that depression and activation of evoked dopamine release in the nucleus caudatus and nucleus accumbens following SD are indicative of tonic activation of the nigrostriatal and tonic inhibition of the mesolimbic dopaminergic terminals by cortex in normal conditions. SD in the cortex, modulating neurotransmitter release in subcortical structures, may have a general impact on redistribution of oxygen supply in these subcortical areas and on behavior associated with brain trauma, migraine, insult or seizures, i.e. the kind of neuropathology which may cause SD type phenomena also in human brain.     

Neuroleptic-like disruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigrostriatal dopamine systems

An examination of the ability to learn an active avoidance response was made in rats subjected to 6-hydroxydopamine (6-OHDA) lesions of the individual terminal areas of the midbrain dopamine (DA) system or a lesion to all these terminal regions in one group. Lesions were made by infusing 8 micrograms (base) of 6-OHDA in 2 microliter of vehicle into the following forebrain regions (each region representing a separate group of rats); frontal cortex, nucleus accumbens, corpus striatum and a double lesion of nucleus accumbens and corpus striatum. A separate group of rats received a smaller 6-OHDA lesion of the ventral substantia nigra. Only those rats with the combined double lesion of both the nucleus accumbens and corpus striatum (90% total depletion of dopamine) showed a severe deficit in acquisition of active avoidance. However, the rats with the separate 6-OHDA lesions to the mesolimbic or nigrostriatal DA systems did show the appropriate blockade of the amphetamine-induced locomotion or stereotyped behavior, respectively. In contrast, the rats with the double lesion showed no response to a low or high dose of amphetamine, remained cataleptic for the duration of the experiment but rapidly recovered from transient aphagia and adipsia (less than 10 days post lesion). Results suggest that a severe deficit in acquisition of an active avoidance response, similar to that observed with high doses of neuroleptics, requires destruction of all of the dopamine innervation of nucleus accumbens and corpus striatum. Results also suggest that both the mesolimbic and nigrostriatal dopamine systems act in concert to produce response enabling to important environmental events, and that the severe response enabling deficits observed in Parkinson's disease involves not only degeneration of the nigrostriatal dopamine system, but of the mesolimbic dopamine system as well.