立体定向毁损大鼠杏仁核及隔核对脑内单胺类递质含量的影响

目的 :探讨杏仁核及隔核毁损后AMP模型大鼠脑内单胺类递质含量的变化。方法 :经腹腔注射苯丙胺 (amphetamine ,AMP)制作精神分裂症动物模型 ,用立体定向技术电极毁损大鼠杏仁核及隔核 ,采用荧光分光光度法和放射免疫法测定大鼠前额叶、间脑和脑干多巴胺 (DA)、5 羟色胺 ( 5 HT)和去甲肾上腺素 (NE)的含量。结果 :杏仁核及隔核毁损组前额叶DA低于模型组 (P <0 0 1) ,5 HT、NE均高于模型组 (P <0 0 1) ;杏仁核及隔核毁损组间脑DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1) ;脑干DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1)。结论 :AMP模型大鼠前额叶和脑干DA含量增高、5 HT和NE含量下降 ,间脑DA、NE含量增高、5 HT含量下降 ,立体定向毁损杏仁核及隔核能够改变脑内单胺类递质的水平。     

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     

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。     

不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响

目的:探讨不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响。方法:建立Wistar大鼠抑郁症模型;分别在模型大鼠双侧颅骨大脑额叶区放置刺激电极(国家发明专利号ZL01103273.1)并固定,应用脑电场刺激仪给予不同强度脑电场刺激,刺激频率30Hz,刺激波形为正弦波,刺激持续时间1h。应用荧光分光光度法分别测定大鼠额叶脑组织内5羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)含量。结果:与正常对照组比,模型对照组大鼠5-HT及NE明显下降(分别P<0.001),治疗对照组单胺类递质无明显变化(分别P>0.05)。低强度治疗组治疗1h后,DA、5-HT及NE含量均无明显改变(分别P>0.05),中等强度治疗组及高强度模型治疗组大鼠额叶脑组织内5-HT及NE含量出现显著增高(分别P<0.05,P<0.01)。结论:一定强度的脑电场刺激可显著提高额叶内单胺类递质的含量,对抑郁症可能提示具有治疗作用。     

性激素对雌性大鼠缰核单胺类递质含量的影响

用高效液相-荧光检测法分别测定了成年及幼年雌性大鼠缰核(Hb)内单胺类递质的含量.结果表明,成年大鼠动情前期缰核内NE含量明显高于动情期和动情间期,DA、5-HT含量在整个动情期中无明显变化.皮下注射50 μg的雌二醇后,缰核内DA含量明显升高,NE、5-HT含量与对照组相比则无明显改变;在去卵巢给以雌激素的大鼠注射孕酮后,可显著提高缰核内NE含量,DA、5-HT含量与对照组比较则无明显变化;在幼年雌性大鼠皮下注射5、50 μg雌激素后,缰核内DA含量显著减少,NE、5-HT含量与对照组相比则均无明显变化.另外,对照组幼年雌性大鼠DA含量明显高于成年雌性大鼠对照组,成年大鼠NE、5-HT含量明显高于幼年大鼠.以上结果提示,雌、孕激素的水平可改变缰核内单胺类递质含量.     

伏隔核毁损对MAP模型大鼠行为及脑内DA受体影响的研究

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80只SpraqueDawley(SD)大鼠随即分为对照组、模型组、假手术组和手术组,每组各20只;采用经腹腔注射MAP制备精神分裂症模型,立体定向-直流电毁损伏隔核,观察大鼠刻板行为变化,原位杂交法观察额叶、颞叶、边缘区及脑干部位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受体表达均显著增加;而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减少。结论伏隔核毁损可能是通过抑制使用MAP而诱发的脑内D2表达的亢进而改变其行为学的异常。     

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     

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.     

帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia

The central neurochemical and neuroendocrine effects of a psychogenic (ferret exposure) and a neurogenic (restraint) stressor were assessed in rats that had been selectively bred for differences in amygdala excitability manifested by either Fast or Slow amygdala kindling epileptogenesis. While these rat lines differ in their emotionality, their behavioral styles were dependent on the nature of the stressor to which they were exposed. During restraint, the Slow rats were mostly immobile, while Fast rats persistently struggled. In contrast, Fast rats were more immobile in response to the ferret. Yet, the more emotional Slow rats exhibited a greater corticosterone response to the ferret, while comparable corticosterone responses between lines were evident following restraint. Although both stressors influenced norepinephrine (NE), dopamine (DA) and/or serotonin (5-HT) activity in brain regions typically associated with stressors (e.g., locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, prefrontal cortex), considerable amine alterations were evident in the medial and basolateral amygdala nuclei, but not in the central nucleus. Moreover, greater NE changes were apparent in the medial amygdala of the left hemisphere. Similarly, DA alterations also were greater in the left medial amygdala in response to stressors. Despite very different behavioral styles, however, the two lines often exhibited similar amine alterations in response to both stressors.     

Prefrontal cortex serotonin, stress, and morphine-induced nucleus accumbens dopamine

Uncontrollable, but not controllable, stress produces a persistent potentiation of morphine-induced nucleus accumbens dopamine (DA) efflux and morphine-induced medial prefrontal cortex serotonin (5-HT) efflux. Here we investigate medial prefrontal cortex 5-HT mediation of this potentiation. Male Sprague-Dawley rats received bilateral medial prefrontal cortex microinjections of the neurotoxin 5,7-dihydroxytriptamine (5,7-DHT, 8 microg/microl/side), which selectively depleted medial prefrontal cortex 5-HT, or vehicle (Sham), and cannula implantation in the nucleus accumbens shell. After 2 weeks, rats received either uncontrollable stress or no stress. Microdialysis and morphine (3 mg/kg) treatment were performed the following day. Morphine produced an enhanced increase in DA in the Stress-Sham group that was completely blocked by 5,7-DHT lesions, suggesting that 5-HT in the medial prefrontal cortex mediates this potentiation.     

Influences of cholecystokinin antiserum on the dopamine,norepinephrine and serotonin contents of different brain regions in rats

The effects of intraventricular administration of cholecystokinin antiserum on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex were tested 24 hr following injection in rats.Cholecystokinin antiserum decreased the DA and NE contents of the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA and decreased the NE content of the striatum. In the cerebral cortex the NE content was decreased. The 5-HT contents decreased in the mesencephalon, amygdala and septum, and increased in the striatum.     

Sensitization to the neuroendocrine, central monoamine and behavioural effects of murine tumor necrosis factor-alpha: peripheral and central mechanisms

Systemic administration of murine tumour necrosis factor-alpha (mTNF-alpha; 0.1-2.0 microg, i.p.) dose-dependently increased plasma corticosterone and augmented monoamine utilization within the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus, medial prefrontal cortex (PFC), central and medial amygdala. A time-dependent sensitization was induced in mice, wherein reexposure to mTNF-alpha 28 days (but not 1 day) following the initial cytokine treatment provoked marked signs of illness (diminished activity, ptosis, piloerection) and increased plasma corticosterone levels. Serotonin (5-HT) activity was augmented upon mTNF-alpha reexposure at the 1- or 28-day intervals in the PFC and medial amygdala, respectively. Intracerebroventricular (i.c.v.; 1-500 ng) mTNF-alpha did not promote illness, but modestly increased plasma corticosterone levels. Neither the illness nor the corticosterone changes were subject to a sensitization upon i.c.v. cytokine reexposure. Acute i.c.v. mTNF-alpha increased norepinephrine (NE), 5-HT and dopamine (DA) activity within the PVN and median eminence/arcuate nucleus complex (ME/ARC), and NE utilization within the central amygdala. Subsequent i.c.v. mTNF-alpha further enhanced the hypothalamic monoamine variations. Finally, systemic (i.p.) mTNF-alpha pretreatment did not proactively influence sickness or corticosterone responses upon later i.c.v. cytokine challenge, but augmented locus coeruleus NE activity and 5-HT and DA utilization within the ME/ARC. It is suggested that the sensitization with respect to sickness and corticosterone activity in response to mTNF-alpha reflect the involvement of peripheral mechanisms. Moreover, it appears that mTNF-alpha promotes central neurochemical plasticity through independent central and peripheral mechanisms.     

In vivo biogenic amine efflux in medial prefiontal cortex with imipramine,fluoxetine, and fluvoxamine

In vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5-HT to a lesser extent. Similar dose-dependent increases in DA and 5-HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5-HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5-HT by the same amount in a dose-dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo. © 1994 Wiley-Liss, Inc.     

5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex

The present study investigated the neurochemical effects of the selective 5-HT(6) receptor antagonist SB-271046 in the rat medial prefrontal cortex (mPFC). The effect of SB-271046 on extracellular levels of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the mPFC was examined using in vivo microdialysis in the freely moving rat. SB-271046 (10 mg/kg, p.o.) produced a significant increase in extracellular levels of both DA and NE without altering 5-HT neurotransmission. These results further support the rationale for the use of 5-HT(6) receptor antagonists in the treatment of cognitive dysfunction associated with psychiatric diseases.     

Influence of cholecystokinin octapeptide sulfate ester on brain monoamine metabolism in rats

Summary The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulfate ester (CCK-8-SE) were tested on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) turnovers of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex in rats.CCK-8-SE in an 80 pmole dose decreased the DA turnovers of the hypothalamus, mesencephalon, amygdala and septum, while it increased that of the striatum. The NE turnovers were increased in the hypothalamus and amygdala, but decreased in the striatum. The 5-HT turnover decreased only in the hypothalamus.     

A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression

Wistar-Kyoto (WKY) rats exhibit hyperresponsive neuroendocrine and behavioral responses to stress that exceed normal controls and are especially prone to develop stress-induced depressive disorder. Pharmacological studies indicate altered serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems functioning in WKY rats, yet no attempt has been made to provide a comprehensive assessment of the neurochemical profile for WKY rats as compared to the outbred progenitor controls, Wistar rats. To this end, male, WKY and Wistar rats (N=6/group) were exposed to an acute forced-swim stress or were left untreated as controls. The prefrontal cortex (PFCtx), striatum, nucleus accumbens (NAS), and amygdala were assayed for levels of NE, DA and 5-HT, as well as major metabolites, by high-pressure liquid chromatography (HPLC) with electrochemical detection. In a separate experiment, designed to assess baseline and stress-induced neuroendocrine activation, male, Wistar and WKY rats (N=6/group) were exposed to an acute forced-swim stress of 15 min or were left untreated as controls. Animals were killed immediately after the test (T=0), 30 min after the test (T=30) or 60 min after the test (T=60), and control animals were killed immediately after weighing. After decapitation, trunk blood was collected and plasma was isolated by centrifugation and analyzed for corticosterone by immunoassay. The neurochemical results demonstrate distinct patterns of baseline and stress-induced monoamine turnover in WKY rats, including alterations to DA and 5-HT turnovers in prefrontal cortex and nucleus accumbens, two critical brain areas implicated in anxiety, depression and drug reward. The neuroendocrine results indicate that WKY rats exhibited a sustained corticosterone response to acute stress, as compared to Wistar controls. Overall, these data are predicted to be useful for understanding the anxiety- and depressive-like behavioral phenotype exhibited by these animals and for increased understanding of the role genetic background in altering neurochemical function.     

Androgen inhibits neurotransmitter turnover in the medial prefrontal cortex of the rat following exposure to a novel environment

Previous studies have demonstrated that gonadal steroid hormones affect the neuroendocrine response to a novel environment and other stressors. Introduction to a novel environment also increases neurotransmitter turnover in the medial prefrontal cortex (MPFC). In this study, we examined the possibility that gonadal steroid hormones could similarly modulate the neurotransmitter response to a novel environment in the MPFC of the male rat. Male Fischer 344 rats at 3 months of age were gonadectomized (GDX'd) and implanted with Silastic capsules containing dihydrotestosterone propionate (DHTP, a non-aromatizable form of androgen), 17 β-estradiol (E), or placebo. Control animals were left intact. Each of these groups was further divided into a group introduced to a novel environment or a home cage control group. Animals exposed to a novel environment were killed after spending 20 min in a novel open field, whereas control animals were killed immediately upon removal from their home cage. Using high performance liquid chromatography, the MPFC was assayed for tissue levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA); norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); or serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). The introduction to a novel environment caused significant increases in turnover of all three neurochemicals examined as estimated by metabolite/precursor ratios. These increases were characterized by increases in DOPAC, HVA, MHPG and 5-HIAA coupled with decreases in DA, NE and 5-HT. There was no effect of GDX on neurotransmitter turnover, however, treatment of GDX animals with DHTP prevented the open field induced increase in DOPAC/DA, MHPG/NE, and 5-HIAA/5-HT ratio. Treatment of GDX animals with estrogen had the opposite effect of DHTP, DOPAC/DA and MHPG/NE ratios increased to a greater level following the introduction to a novel environment than in GDX or intact animals. Examination of behavior in the open field showed significant decreases in activity in the DHTP-treated group but not in any other behavioral parameter (rears, nose pokes). Since the non-aromatizable androgen, DHTP, is presumably acting via androgen receptors, and E is presumably acting via estrogen receptors, these data suggest that, in the MPFC of male rats, androgen and estrogen receptors act in an opposing fashion to modify neurotransmitter turnover. This suggests that local changes in the relative levels of androgen and estrogen can have profound effects on the neurobiological response of the medial prefrontal cortex to stimuli.© 1997 Elsevier Science B.V. All rights reserved.