Lesions of the nucleus accumbens shell can reduce activity in the elevated plus-maze

Across different behavioural tasks, nucleus accumbens (n.acc) lesions have generated conflicting effects on locomotor activity and in particular, the relative roles of the n.acc shell and core subfields in this have been controversial. To date there is only one study examining effects of lesions to the medial n.acc on elevated plus-maze (EPM) behaviour; these lesions were shown to increase both locomotor and exploratory activity. Given the well-documented distinction between shell and core, the present study sought to extend previous research by testing lesions selective to each n.acc subfield in the EPM. Results showed no statistical differences between core lesioned and sham-operated animals on any measure. In contrast, shell lesions consistently reduced locomotion and exploratory activity. This direction of effects is opposite to that previously observed after medial n.acc. lesions. In conclusion, locomotion and exploratory activity were clearly reduced by shell but not core lesions, consistent with other evidence for the functional heterogeneity of n.acc shell and core.     

Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopy

In positron emission tomography and single photon emission computed tomography studies using D2 dopamine (DA) receptor radiotracers, a decrease in radiotracer binding potential (BP) is usually interpreted in terms of increased competition with synaptic DA. However, some data suggest that this signal may also reflect agonist (DA)-induced increases in D2 receptor (D2R) internalization, a process which would presumably also decrease the population of receptors available for binding to hydrophilic radioligands. To advance interpretation of alterations in D2 radiotracer BP, direct methods of assessment of D2R internalization are required. Here, we describe a confocal microscopy-based approach for the quantification of agonist-dependent receptor internalization. The method relies upon double-labeling of the receptors with antibodies directed against intracellular as well as extracellular epitopes. Following agonist stimulation, DA D2R internalization was quantified by differentiating, in optical cell sections, the signal due to the staining of the extracellular from intracellular epitopes of D2Rs. Receptor internalization was increased in the presence of the D2 agonists DA and bromocriptine, but not the D1 agonist SKF38393. Pretreatment with either the D2 antagonist sulpiride, or inhibitors of internalization (phenylarsine oxide and high molarity sucrose), blocked D2-agonist induced receptor internalization, thus validating this method in vitro. This approach therefore provides a direct and streamlined methodology for investigating the pharmacological and mechanistic aspects of D2R internalization, and should inform the interpretation of results from in vivo receptor imaging studies.     

柴胡对肝郁证中枢神经递质作用的实验研究

目的探索柴胡对肝郁证大鼠中枢神经递质的作用。方法利用中医证候模型,研究柴胡对单胺类神经递质的作用。结果肝郁证模型组大鼠脑内NE与DA水平与对照组比较下降明显(P<0.05);肝郁证模型加逍遥散组大鼠脑内NE与DA水平与对照组比较无显著性差异(P>0.05);肝郁证模型加柴胡组大鼠脑内NE与DA水平与对照组比较也无显著性差异(P>0.05)。结论肝郁证大鼠脑内NE与DA水平明显降低,柴胡舒肝解郁,有增加肝郁证大鼠脑内NE、DA神经递质的作用。     

人羊膜上皮细胞侧脑室移植对帕金森病大鼠模型行为、多巴胺能神经元、神经递质影响的实验研究

目的 观察人羊膜上皮细胞(HAECs)移植入帕金森病(PD)大鼠模型侧脑室后的存活及分化情况,及其对PD大鼠模型旋转行为、纹状体区多巴胺及其代谢产物的影响.方法 采用6-羟多巴立体定向脑内注射制作PD大鼠模型,将制模成功大鼠随机分成3组:人羊膜上皮细胞移植组(HAECs组)、磷酸缓冲组(PBS组)和帕金森组(PD组),1w后腹腔注射阿朴吗啡观察各组大鼠旋转行为的变化,连续观察10w,HAECs组5w后用人特异性抗体Nestin和Vimentin检测人羊膜细胞的存活情况,10w后酪氨酸羟化酶(TH)染色观察各组PD大鼠模型黑质部TH阳性神经元的变化情况及HAECs的分化情况,高效液相色谱--电化学仪测定纹状体多巴胺(DA)、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)等神经递质的水平.结果 HAECs在PD大鼠侧脑室内移植可以长期存活达10w,并且可以分化为DA能神经元,HAECs组大鼠旋转数较PBS组及PD组明显降低(P<0.01),黑质部TH阳性神经元数量较PD组及PBS组升高(P<0.01),HAECs组大鼠纹状体区DA及其代谢产物DOPAC、HVA含量较PBS组明显升高(P<0.05).结论 人羊膜上皮细胞移植入PD大鼠侧脑室可以改善PD大鼠的旋转行为,其机制可能与增加纹状体区DA等神经递质有关.     

Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease

Ethnopharmacological relevance

While the Hibiscus asper Hook.f. (Malvaceae) is a traditional herb largely used in tropical region of the Africa as vegetable, potent sedative, tonic and restorative, anti-inflammatory and antidepressive drug, there is very little scientific data concerning the efficacy of this.

Aim of the study

We investigated antioxidant activity and the effects of methanolic extract of Hibiscus asper leaves on neurological capacity of male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion.

Materials and methods

Two model systems: 2,4-dinitrophenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and β-carotene bleaching inhibition assay were used to measure the antioxidant activities of the plan extract. We also investigated the neuroprotective effect of methanolic extract of Hibiscus asper leaves (50 and 100 mg/kg) in male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion rat model.

Results

Methanolic extract of Hibiscus asper leaves showed potent antioxidant and free radical scavenging activity. Chronic administration of methanolic extract (50 and 100 mg/kg, i.p., daily, for 7 days) significantly reduce anxiety-like behavior and inhibit depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation.

Conclusions

Taken together, our results suggest that the methanolic extract of Hibiscus asper leaves have antioxidant effects and might provide an opportunity to management neurological abnormalities in Parkinson's disease conditions.     

Involvement of interleukin 18 in indomethacin-induced lesions of the gastric mucosa in adjuvant-induced arthritis rat

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAIDs-induced gastric lesions in comparison with other patients. The pathogenic mechanism of these lesions is not fully understood. We demonstrate whether interleukin 18 (IL-18) expression relate the aggravation of gastric lesion in adjuvant-induced arthritis (AA) rats following the oral administration of indomethacin. Arthritis was induced by injecting 50 microl of a suspension of 10mg/ml heat-killed butyricum (Mycobacterium butyricum) in Bayol F oil into the plantar region of the right hind foot and tail of Dark Agouti rats resulting in an arthritis incidence of 100%. Two weeks after injection, the rats were administered indomethacin (40mg/kg) orally, and were killed under deep ether anesthesia 6h later. The gastric mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the gastric mucosa of AA rats, and the lesion score for AA rats following indomethacin treatment was significantly higher than for normal rats administered indomethacin. The expression of the IL-18 mRNA and mature IL-18 protein in the gastric mucosa of AA rats administered indomethacin were also higher in comparison with normal rats receiving indomethacin. In addition, interferon-gamma and nitric oxide levels in the gastric mucosa of AA rats were increased by the oral administration of indomethacin. It is possible that IL-18 expression in AA rats is more sensitive to indomethacin, and the IL-18 may play a role in the aggravation of gastric lesions in AA rats treated with indomethacin.     

Cannabis, cocaine, and visuomotor integration: evidence for a role of dopamine D1 receptors in binding perception and action

The primate cortex represents and produces events in a distributed way, which calls for a mechanism that integrates their features into coherent structures. Visuomotor integration seems to be driven by dopaminergic (DA) pathways but which subsystems are involved is currently unknown. The present study compared the impact of the recreational use of two drugs on visuomotor integration: cannabis, which primarily targets dopaminergic D1 receptors, and cocaine, which mainly targets D2 receptors. Our findings show that cannabis but not cocaine use affects the strength of the binding between task-relevant stimulus features and the accompanying response. In contrast, cocaine but not cannabis use eliminates the inhibition of return. The observed pattern suggests that visuomotor integration is driven by DA/D1, but not DA/D2 receptor systems.     

The possible role of retinal dopaminergic system in visual performance

It is a well-known fact that the retina is one of the tissues in the body, which is richest in dopamine (DA), yet the role of this system in various visual functions remains unclear. We have identified 13 types of DA retinal pathologies, and 15 visual functions. The pathologies were arranged in this review on a net grid, where one axis was “age” (i.e., from infancy to old age) and the other axis the level of retinal DA (i.e., from DA deficiency to DA excess, from Parkinson disorder to Schizophrenia). The available data on visual dysfunction(s) is critically presented for each of the DA pathologies. Special effort was made to evaluate whether the site of DA malfunction in the different DA pathologies and visual function is at retinal level or in higher brain centers. The mapping of DA and visual pathologies demonstrate the pivot role of retinal DA in mediating visual functions and also indicate the “missing links” in our understanding of the mechanisms underlying these relationships.     

Cytochrome P450 2E1 in the substantia nigra: relevance for dopaminergic neurotransmission and free radical production

Cytochrome P450 2E1 (CYP2E1) has been detected in brain regions which are of relevance for the pathophysiology of Parkinson's disease, such as the substantia nigra (SN). Furthermore, CYP2E1 is known to generate reactive oxygen species (ROS), toxic molecules which have been implicated in the pathogenesis of the disease. We have previously reported that CYP2E1 inhibition increases extracellular dopamine (DA) in the SN. The aims of the present study were by using in vivo microdialysis in rat, to elucidate the mechanisms responsible for the increase in extracellular DA induced by CYP2E1 inhibition and to explore whether ROS is produced in the SN, both with and without the presence of an exogenous CYP2E1 substrate. The effect of inhibition of CYP2E1 by phenylethyl isothiocyanate (100 mg/kg) on extracellular DA in the SN was unaltered following pretreatment with gamma-butyrolactone and GBR-12909, drugs that inhibit firing of DA neurons and DA re-uptake, respectively. Preadministration of tetrodotoxin or reserpine, however, abolished the effect of CYP2E1 inhibition. Administration of isoflurane, an anesthetic which is metabolized by CYP2E1, increased the production of *OH in the SN, as measured by the transformation of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid during local perfusion compared with animals given other anesthetics. The results support the notion that CYP2E1 is located near or in the same compartment in the SN as stored DA, tentatively the endoplasmatic reticulum, and that the enzyme activity might modulate the amount of DA that is available for release. Furthermore, our findings indicate that the production of ROS can be stimulated by CYP2E1 substrates.