Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.

Relationship between electroacupuncture analgesia and dopamine receptors in nucleus accumbens

目的：研究多巴胺受体拮抗剂左旋四氢巴马汀（ｌＴＨＰ）加强电针镇痛（ＥＡＡ）的原理，阐明中枢神经系统内多巴胺（ＤＡ）系统在ＥＡＡ中的作用．方法：分别将Ｄ１受体激动剂ＳＫ＆Ｆ３８３９３和Ｄ２受体激动剂ｑｕｉｎｐｉｒｏｌｅｈｙｄｒｏｃｈｌｏｒｉｄｅ（Ｑｕｉ）注射入大鼠伏膈核，观察对ＥＡＡ及ｌＴＨＰ加强ＥＡＡ的作用．结果：ＳＫ＆Ｆ３８３９３（５μｇ，１０μｇ）明显对抗了ｌＴＨＰ加强ＥＡＡ的作用，１０μｇＳＫ＆Ｆ３８３９３则减弱ＥＡＡ；Ｑｕｉ（１０μｇ，２０μｇ），对ＥＡＡ及ｌＴＨＰ加强ＥＡＡ的作用没有显著影响．结论：伏膈核内Ｄ１受体活动在ＥＡＡ及ｌＴＨＰ加强ＥＡＡ中起重要作用，Ｄ２受体没有显著作用．

Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain

Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.

Effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization in high myopia mice

AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.

New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease

The neurotransmitter dopamine acts via two major classes of receptors, Dl-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains： L-DOPA-induced dyskinesias in Parkinson＇s disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective Dl-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, aUosteric modulators, or by making targeted modifications to Dl-receptor machinery. The development of therapies specific to Dl-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.

氯胺酮快速抗抑郁机制及不良反应的研究进展

目的对氯胺酮治疗抑郁症的可能作用机制及临床不良反应进行系统阐述,以期为氯胺酮的临床研究及新一代抗抑郁药的研制提供思路及参考。方法从中国知网(CNKI)、万方中文数据库、Web of Science数据库及PubMed数据库检索2012年5月至2022年5月收录的相关文献;以“氯胺酮、艾司氯胺酮、抑郁症、难治性抑郁症、重度抑郁症、N-甲基-D-天冬氨酸受体、α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体、脑源性神经营养因子、雷帕霉素靶蛋白、肠道菌群、真核延伸因子2激酶、不良反应”为中文检索词,以“ketamine,esketamine,depression,treatment resistant depression,major depressive disorder,NMDAR,AMPAR,BDNF,TOR,gut microbiota,eEF2K,side effect”为英文检索词,最终纳入83篇文献进行研究分析。结果与结论氯胺酮是一种N-甲基-D-天冬氨酸受体(N-methyl-d-aspartate receptors,NMDAR)拮抗剂,由(S)-氯胺酮和(R)-氯胺酮两种对映异构体按照1∶1的比例构成。已有证据表明其对抑郁症的治疗有着显著疗效。研究显示,氯胺酮的作用机制可能与NMDAR、α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor,AMPAR)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、肠道菌群、真核延伸因子2激酶(eukaryotic elongation factor 2 kinase,eEF2K)等有关。同时,多项研究显示氯胺酮可能导致神经毒性反应、拟精神病、心血管系统疾病,以及泌尿系统疾病等多种不良反应,导致其在临床应用及试验中存在一定局限性。因此,深入探讨氯胺酮的作用机制及临床不良反应应,探索氯胺酮可能的作用靶点极其重要。

Aβ42寡聚体对突触内外谷氨酸受体表达的影响

目的:通过体内外实验探讨阿尔茨海默病关键发病分子β-淀粉样蛋白42寡聚体(Aβ42Os)作用下离子型谷氨酸受体N-甲基-D-天冬氨酸受体(NMDAR)亚基(NR2A、NR2B和NR1)和代谢型谷氨酸受体5(mGluR5)在突触内外的表达分布变化。方法:(1)用不同浓度的Aβ42Os处理乳小鼠原代神经元,Western blot和免疫荧光染色检测原代神经元中mGluR5和NMDAR的表达和分布情况。(2)在C57BL/6小鼠侧脑室立体定位注射不同浓度的Aβ42Os,Western blot检测海马组织中mGluR5和NMDAR在突触内外的蛋白水平,以及mGluR5下游磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/AKT)信号通路相关蛋白、钙信号下游通路相关蛋白和突触相关蛋白的表达。结果:(1)高浓度Aβ42Os处理原代小鼠神经元增加mGluR5表达(P<0.01),减少NR2A、NR2B和NR1表达(P<0.01);引起mGluR5膜表面聚集,而使NR2A、NR2B和NR1膜表面表达分布减少。(2)高浓度Aβ42Os引起小鼠海马组织中突触mGluR5表达增加(P<0.01),NR2A(P<0.05)和NR2B(P<0.01)表达减少,突触外NR2B表达增加(P<0.01);抑制PI3K表达及AKT和细胞外信号调节激酶(ERK)磷酸化,过度激活钙/钙调蛋白依赖性蛋白激酶IIα(CaMKIIα);引起突触后致密蛋白95、亲棘蛋白(spinophilin)、突触小泡蛋白(synaptophysin)和微管相关蛋白2表达减少(P<0.01)。结论:(1)高浓度Aβ42Os引起神经元突触mGluR5过度聚集,NR2A、NR2B和NR1表达减少,而突触外NR2B表达增加。(2)高浓度Aβ42Os抑制PI3K/AKT和ERK信号通路,过度激活CaMKIIα通路,损伤突触结构。

The hypothalamic-spinal dopaminergic system:a target for pain modulation

Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise,among others, noradrenergic, serotonergic, γ-aminobutyric acid(GABA)ergic, and dopaminergic fibers.The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood.The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.

Dopamine: an immune transmitter

The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.

The dopamine receptor D4 regulates the proliferation of pulmonary arteries smooth muscle in broilers by downregulating AT1R

The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells(VSMCs),and one of the main causes of pulmonary hypertension syndrome(PHS)in broilers is pulmonary artery vascular remodeling.Forty Arbor Acres(AA)broilers were randomly divided into four groups(n=10):a control group(deionized water,Og/L NaCl),a freshwater group(FW,deionized water+1 g/L NaCl),highly salinized freshwater group 1(H-SFW-1,deionized water+2.5 g/L NaCl)and highly salinized freshwater group 2(H-SFW-2,deionized water+5 g/L NaCl).The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water(H-SFW-1&H-SFW-2),which significantly increased the content of angiotensin II(Ang II)and the expression of angiotensin II type 1(AT1)receptor protein.Meanwhile,it significantly decreased the expression of dopamine receptor D4(DRD4)protein.The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers,which could be significantly inhibited by DRD4 agonists(D4A,HY-101384A)and enhanced by DRD4 inhibitors(D4I;HY-B0965).In addition,the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers,either at the transcriptional or translational level.At the same time,the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A.The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner.These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers,accompanied by varying degrees of proliferation of pulmonary artery smooth muscle.This mechanism may involve response of its receptor being induced by increased Ang II,while DRD4 can negatively regulate it.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

-94 G/A polymorphism in the dopamine D1 receptor gene is associated with schizophrenia in a Chinese Han population from Shandong province

The correlation between -94 G/A polymorphism in the dopamine D1 receptor gone and schizophrenia remains poorly understood despite extensive research. This study sought to evaluate the genotypes and allele frequencies of the -94 G/A polymorphism in the dopamine D1 receptor gone by real-time PCR using TaqMan fluorescent probes. One hundred and sixty-two patients with schizophrenia and 101 healthy controls living in Shandong province of China were evaluated. Experimental results showed that the G/A genotype distribution was significantly higher in the schizophrenia patients than in healthy controls. The frequencies of G allele and A allele were not significantly different between the schizophrenia patients and the controls. Thus, the -94 G/A polymorphism in the dopamine D1 receptor gone was found to be associated with schizophrenia in a Chinese Han population from Shandong province.

Dopamine receptor D3R and D4R mRNA levels in peripheral lymphocytes in patients with schizophrenia correlate with severity of illness

Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.

Down-regulation of dopamine D2 receptor associates with impaired reversal learning induced by morphine withdrawal

OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study examined the impact of morphine withdrawal on reversal learning.METHODS Reversal learning was tested in a four-choices digging task.Some brain tissues were harvested 2 h after the behavioral experiment for the further measurement.RESULTS We found that after long-term abstinence for a month from chronic morphine exposure,mice exhibited a profound reversal learning deficit.We further found that dopamine D2 receptor(D2R)system in the frontal-striatal circuit is significantly down-regulated,at both receptor and downstream signals levels.Subsequent pharmacological experiments demonstrated that aripiprazole,a D2R partial agonist,prevented the D2R downregulation and rescued the reversal learning deficit.CONCLUSION Together,our findings provide valuable insights into the causal relationship between D2R system in the frontal-striatal circuit and the cognitive inflexibility caused by abused drugs and offer a promising possibility of an effective therapeutic intervention for drug addictions.

Anti-post-traumatic stress disorder effect of dopamine D3 receptor antagonist

OBJECTIVE To explore the antipost-traumatic-stress-disorder(PTSD) effects and its probable mechanism of YQA14,a dopamine D3 receptor antagonist.METHODS Two PTSD animal models,the rat single prolonged stress(SPS) model and the mouse pre-shock model,were used in this experiment.In the SPS model,adult male Sprague-Dawley(SD) rats were randomly divided into control group,model group,positive group and YQA14 groups with different dosages.In the mouse pre-chock model,dopamine D3 receptor knockout(KO) and wild type(WT) mice were randomly divided into control group,model group,positive group and YQA14 group.After the establishment of animal models,the saline,sertraline(ig) and YQA14(ip)were administered to the animals in the control,model,positive control and test groups respectively.The open field test(OFT) was used to evaluate the locomotor activity while the contextual freezing(CF) measurement and elevated plus maze(EPM) test were used to evaluate the PTSD-like behaviors.RESULTS In the rat SPS model,neither SPS nor drug treatment affected the locomotor activity in rats.However,SPS rats showed significant PTSD-like behaviors with enhanced freezing time in CF(P<0.01) and decreased percentage of entries into open arms and time spent in open arms in EPM(P<0.05,P<0.01).Moreover,compared with the model group,the repeated administration of YQA14(3.125,6.25 and 12.5 mg·kg-1)significantly reduced the freezing time(P<0.01)and increased the percentages of entries into open arms and time spent in open arms(P<0.05).In the mouse pre-shock model,when both model groups showed significant higher freezing time compared with the respective control groups(P<0.05,P<0.01),YQA14 selectively alleviated the freezing time on WT mice(P<0.05) while had no effect on KO mice.In the EPM tests,the WT mice model group showed a significant reduction in the percentage of entries into open arms and time spent in open arms(P<0.05) while D3 R KO mice model group didn′ t show any reduction,compared with respective control groups.Furthermore,daily administration of YQA14 at 12.5 mg·kg-1 both significantly reduced the percentages of entries into and time spent in open arms(P<0.05) but not D3 R KO mice.None of the locomotor activity were significantly affected.CONCLUSION YQA14 could significantly alleviate the PTSD-like behaviors in rodents and the effects were mediated by the blockade of brain D3 receptors.

Effects of septal nucleus lesion on dopamine D_2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia

BACKGROUND： It has been demonstrated that the septal nucleus is involved in the pathogenesis of schizophrenia. Based on autopsies of schizophrenia patients, studies have shown a reduced number of septal nucleus neurons and glia. In addition, experimental rat models of schizophrenia have shown increased dopamine receptor D2 binding sites in the basal ganglia, septal nuclei, and substantia nigra. Previous studies have demonstrated that the septal nucleus modulates dopamine metabolic disorder and dopamine D2 receptor balance. OBJECTIVE： Dopamine D2 receptor expression in a rat model of schizophrenia, combined with antipsychotic drugs, was analyzed in the prefrontal lobe, striatum, and brainstem. In situ hybridization was used to observe the effects of stereotactic septal nucleus lesions on dopamine D2 receptor expression in the brains of methylamphetamine-treated rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed in the Laboratory of General Institute of Psychosurgery, Third Hospital of Chinese PLA from November 2005 to June 2006. MATERIALS： A total of 120 healthy, adult Sprague Dawley rats, weighing approximately 200 g, were included. Methylamphetamine （Sigma, USA） and an in situ hybridization detection kit for dopamine D2 receptor （Boster, China） were also used for this study. METHODS： All rats were randomly allocated to the following 4 groups, with 30 rats in each group： normal control, simple administration, septal nucleus lesion, and sham-operated groups. In the normal control group, rats were not administered or lesioned. In the remaining 3 groups, rats were intraperitoneally administered 10 mg/kg methylamphetamine, once per day, for 15 successive days to establish a schizophrenia model. Following successful model establishment, rats from the septal nucleus lesion group were subjected to stereotactic septal nucleus lesions. The cranial bone was exposed in rats from the sham-operated group, and the septal nucleus was not lesioned. MAIN OUTCOME MEASURES： At 7 days post-surgery, dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem were detected by in situ hybridization. RESULTS： Dopamine D2 receptor expression in the rat prefrontal lobe, striatum, and brainstem was significantly higher in the simple administration group and sham-operated group, compared with the normal control group （P 〈 0.01）. In the septal nucleus lesion group, dopamine D2 receptor expression was significantly less than the simple administration and sham-operated groups, （P 〈 0.01）. There was no significant difference in dopamine D2 receptor expression between the simple administration and sham-operated groups （P 〉 0.05）. CONCLUSION： Septal nucleus lesions reduce dopamine D2 receptor expression in the prefrontal lobe, striatum, and brainstem in a rat model of schizophrenia, indicating that the septal nucleus modulates dopamine D2 receptor expression.

Dopamine receptor D4 gene (DRD4) is associated with gazing toward humans in domestic dogs (<i>Canis familiaris</i>)

Dogs show high social communicative ability in interactions with humans. We investigated the association between dogs’ social communicative behavior and the polymorphisms of a gene related to a neurotransmitter. We used an “unsolvable task”, in which an experimenter put a food reward into a container and closed it firmly so that dogs could not remove the reward. Human-directed gazing, possibly to request help, is a characteristic behavioral trait of dogs in such situations. The association between owner-directed gazing behavior in the unsolvable task and polymorphisms of three regions (exon1, exon3, intron2) in the dopamine receptor D4 gene (DRD4) was analyzed. We found that the genotype of DRD4 intron2 was significantly associated with the dogs’ gazing behavior. Dogs carrying shorter allele (P) looked at their owner more frequently, for longer, and earlier than dogs carrying longer allele (Q). This result suggests that polymorphism in DRD4 intron2 may affect social communication and cognition in dogs.

血清CC类趋化因子配体5、维生素D受体表达水平与产后抑郁的关系

目的:探讨产后抑郁症患者血清CC类趋化因子配体5(CCL5)、维生素D受体(VDR)与产后抑郁的相关性。方法:选择2020年12月至2022年4月在西北妇女儿童医院分娩的67例产后抑郁症患者作为观察对象(抑郁组),另选择同期分娩后无抑郁症的70例产妇作为对照组,比较两组血清CCL5、VDR水平,分析CCL5、VDR与爱丁堡产后抑郁量表(EPDS)及汉密顿抑郁量表(HAMD)评分相关性。结果:抑郁组患者血清CCL5水平显著高于对照组,VDR水平显著低于对照组(P<0.05);抑郁组患者血清CCL5水平与EPDS评分、HAMD评分均呈正相关(r=0.468、0.595,P均<0.05),血清VDR水平与EPDS评分、HAMD评分均呈负相关(r=-0.549、-0.671,P均<0.05);CCL5≥101.13 ng/L、VDR<31.17 ng/mL是产后抑郁的影响因素(P均<0.05);血清CCL5、VDR单独及联合辅助诊断产后抑郁的曲线下面积(AUC)分别为0.846、0.825、0.931。结论:血清CCL5水平升高、VDR水平降低与产后抑郁发生密切相关,二者联合对产后抑郁有一定辅助诊断价值。

多巴胺D_2受体TaqIA多态性与海洛因依赖行为相关性

目的 :探讨多巴胺 (DA)受体D2 亚型基因TaqIA多态性与海洛因依赖者行为之间的相关性。方法 :应用PCR -RFLP法对 6 6例海洛因依赖病人与 132例正常人D2 R基因的TaqIA多态性特征进行对照研究。以A型行为问卷 (TABPQ) [1] 测评海洛因依赖者的行为类型 ,与其TaqIA多态性特征进行相关分析。结果 :海洛因依赖组与正常对照组DRD2 基因的TaqIA多态性基因型及等位基因频率有显著性差异 (前者携带A1等位基因的频率为 0 6 1,后者携带A1等位基因的频率为 0 31,P <0 0 5 ) ,携带A1等位基因更易形成海洛因依赖者 (比值比OR :3 47,P <0 0 5 )。各种行为类型的海洛因依赖者之间 ,基因型 (TaqIA多态性 )无显著性差异 (P >0 0 5 )。结论 :多巴胺D2 受体基因的TaqIA多态性与海洛因依赖相关连。多巴胺D2 受体基因TaqIA多态性与海洛因依赖者成瘾性的形成可能相关。这种基因位点特征可能与其他候选基因及环境因素共同作用 。