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Objective To investigate the topographic distributions of dopamine transporter (DAT),dopamine D2 receptor and glucose in Parkinson's disease (PD) and multiple system atrophy (MSA) using positron emission tomography/computed tomography (PET/CT) scanning and statistical parametric mapping (SPM) analysis.Methods Seventy subjects (39 PD patients,15 MSA patients and 16 normal controls) who came from People's Liberation Army General Hospital from September 2013 to November 2015 underwent DAT,D2 receptor and glucose brain PET/CT scans using 11 C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (11C-β-CFT),11C-raclopride and 18F-fluorodeoxyglucose (18 F-FDG) as radiotracers,respectively.The uptake patterns were analyzed using SPM software.Results Striatal DAT binding decreased in the putamen in PD patients compared with controls (Z =5.21-5.77,P =0.002-0.016).D2 receptor showed no significant differences.However,glucose uptake decreased in cingulate gyrus(Z =4.51-4.67,P =0.010-0.017).For MSA patients,both DAT and D2 receptor binding decreased in the putamen(Z =2.13-3.42,P =0.000-0.016).Glucose uptake decreased in the bilateral putamen,cerebellum and part of frontal temporal lobes (Z =1.86-3.75,P =0.000-0.032).Conclusion Multiple modalities PET/CT scans using the ligands 11 C-β-CFT,11C-raclopride,and 18F-FDG are valuable in diagnosis of MSA and differential diagnosis of MSA from PD.
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Dopamine supersensitivity psychosis (DSP) is a type of acute exacerbation of recurrent psychosis caused by long-term treatment with antipsychotics in schizophrenic patients. Although DSP is exceedingly troublesome for clinicians, effective treatment has not yet been established. Based on clinical research and our animal study, we hypothesize that aripiprazole, an atypical anti-psychotic, may reduce the exacerbation of recurrent psychotic episodes. We report the case of a 46-year-old female who suffered from schizophrenia with DSP. In this case, sustained treatment with a high dose of aripiprazole gradually reduced the severity of her recurrent psychotic episodes. In conclusion, sustained treatment with aripiprazole may reduce the exacerbation of recurrent psychotic episodes in schizophrenic patients with DSP, and may be an effective treatment of DSP.
Subject(s)
Animals , Female , Humans , Middle Aged , Antipsychotic Agents , Aripiprazole , Disease Progression , Dopamine , Psychotic Disorders , Receptors, Dopamine D2 , Recurrence , SchizophreniaABSTRACT
Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.
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Objective To evaluate the role of spinal dopamine D2 receptors in a rat model of neuropathic pain.Methods Thirty healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-200 g,wcre randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),sham operation group (group S),neuropathic pain group (group NP),normal saline group (group N) and dopamine D2 receptor agonist quinpirole group (group Q).Neuropathic pain was produced by chronic constriction injury of the sciatic nerve (CCI) in rats anesthetized with intraperitoneal 2％ pentobarbital sodium 40 mg/kg.At 7 days after CCI,normal saline 10 μl was injected intrathecally over 30 s in group N,and quinpirole 10 μg (in 10 μl of normal saline) was injected intrathecally over 30 s in group Q.At 1 day before CCI,3 and 7 days aher CCI,and 30 min and 1,2,4,8 and 16 h after administration,mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.Results There was no significant difference in MWT and TWL at each time point between group C and group S.MWT was significantly lower,and TWL was shorter at T1-8 in NP,N and Q groups than in C and S groups.Compared with group N,no significant change was found in MWT and TWL at each time point in N group,and MWT was significantly increased,and TWL was prolonged at T4-6 in group Q.Conclusion Inhibited function of spinal dopamine D2 receptors is involved in the maintenance of neuropathic pain in rats.
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OBJECTIVE To study mechanisms of terguride on the treatment of herion dependence. METHODS Adult male SD rats were randomly assigned into 5 groups: normal control group, saline treatment during heroin use period group, terguride treatment during heroin use period group, saline treatment during heroin reinstatement period group, terguride treatment during heroin reinstatement period group, the last 4 groups established heroin intravenous self administration and cue induced reinstatement models, and after interfernce and perfusion to get the following five brain regions [including ventral tegmental area (VTA)]sections. The expression of dopamine D2 receptor protein and mRNA, prodynorphin protein and preprodynorphin mRNA was detected by immunohistochemistry and hybridization in situ. RESULTS The expression of dopamine D2 receptor was downregulated during heroin use period and upregulated during heroin reinstatement period in nucleus accumbens shell (AcbSH) region, the expression of dopamine D2 receptor mRNA was parallelled with the protein expression approximately, terguride could downregulate the high expression of receptor protein during reinstatement. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin reinstatement period in central nucleus amygdalae (CeA) region, and terguride could downregulate this high expression. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin use period and downregulated during heroin reinstatement period in CA1 region of hippocampus and prefrontal cortex (PFC), terguride could downregulate the high expression of mRNA during heroin reinstatement period. The expression of dynorphin protein and mRNA was upregulated during heroin reinstatement period, terguride could downregulate this high expression. The expression of dynorphin protein was upregulated during heroin reinstatement period, and terguride could downregulate this high expression. CONCLUSION The activity of mesolimbic dopamine is boosted up during heroin use period and depressed during reinstatement period, terguride can regulate this dysregulation. The activity of dynorphin is boosted up during cue induced reinstatement, and terguride has the downregulation effect. So the preclinic study demonstrated that terguride has the potential benefit in heroin dependence.
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OBJECTIVES: The purpose of the present study was to investigate whether the Taq I A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. METHODS: DRD2 Taq I A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. RESULTS: The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. CONCLUSION: No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.
Subject(s)
Humans , Alleles , DNA , Dopamine , Genotype , Polymorphism, Restriction Fragment Length , Receptors, Dopamine , Receptors, Dopamine D2 , Tic Disorders , Tics , Tourette SyndromeABSTRACT
AIM: To observe the effects of different doses of L-dopa on the rotational behavior and amounts of cells expressing D_2 receptors in striatum in hemiparkinsonian rats.METHODS: A hemiparkinsonian model was established in rats by pretreatment with 6-hydroxydopamine.The D_2 receptor expression were detected by immunohistochemical staining.The numbers of rotations induced by apomorphine was counted within 30 min before and after L-dopa(10 mg?kg~(-1)?d~(-1),50 mg?kg~(-1)?d~(-1) or 100 mg?kg~(-1)?d~(-1),ip) was introduced to Parkinson's disease(PD) model rats for 15 days.RESULTS: In successful PD model rats,the increased percentage of D_2 receptor in lesioned side compared with intact side was associated linearly with the numbers of rotations within 30 min(r=0.927,P