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1.
Ten unmedicated and ten medicated patients with major depression and ten controls were investigated with IBZM-SPECT. The ten unmedicated patients were reinvestigated after treatment with tricyclic antidepressants. Dopamine D2 receptor occupancy was not different between patients and controls, or medicated and unmedicated patients. IBZM binding was increased in four patients with psychomotor retardation. Antidepressant therapy led to a decrease in IBZM binding in the five improved patients. Dopamine D2 receptor binding remained unchanged in nonresponders. It is concluded that striatal dopamine D2 receptor binding is not changed in depression or by tricyclic antidepressants; however, it is affected by psychomotor activity. The changes observed might be the result of increased tonic dopamine release in the basal ganglia, but several other explanations exist. 相似文献
2.
R. T. Malison Elinore McCance Linda L. Carpenter Ronald M. Baldwin John P. Seibyl Lawrence H. Price Thomas R. Kosten Robert B. Innis 《Psychopharmacology》1998,137(4):321-325
The in vivo potency of mazindol for binding to striatal dopamine transporters (DAT) was assessed by [123I]β-CIT ([123I]2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT). Cocaine-dependent subjects
(n=12) underwent three SPECT scans; one before, between, and after subchronic (1 week) administration of 2mg/day and 4mg/day
mazindol. For each scan, subjects were injected with [123I]β-CIT and imaged 24h later under equilibrium conditions. Results showed a statistically significant main effect of mazindol
dose (df=2, F=10.30, P<0.001, repeated measures ANOVA) in reducing the specific to non-displaceable equilibrium partition coefficient, V3″ (a measure proportional to DAT binding potential). Regression analysis of the logit transformed data enabled estimation
of the 50% displacement dose of mazindol (ED50 =30mg/ day). These data suggest that low doses of mazindol (i.e., 2–4mg) occupy a small percentage (i.e., <25%) of DAT in
human cocaine abusers and that much higher, potentially intolerable doses (i.e., ≥30mg/day) may be required to antagonize
significantly cocaine binding in vivo.
Received: 14 November 1996/Final version: 17 December 1997 相似文献
3.
目的在中国汉族人群中探讨控制生活事件、人格的发病风险后,去甲肾上腺素转运体(NET)基因G1287A基因多态性与重性抑郁症(MD)的关联性。方法本研究采用年龄、性别1∶1配对病例对照研究设计。病例组为符合《精神疾病诊断与统计手册》第四版(DSM-Ⅳ)的重型抑郁障碍患者98例,并经汉密顿抑郁量表(HAMD)、抑郁自评量表(SDS)、遗传学研究用诊断检查(DIGS)筛查。对照组为来自同地区社会健康自愿人群98名。2组入组前均测试生活事件量表(LES)、艾森克个性问卷(EPQ)。基因多态性的实验测定使用焦磷酸测序仪PSCE96MA检测法。统计分析基因型、等位基因、EPQ个性纬度的相对危险度(OR)以及控制生活事件、人格对MD发病风险后的调整OR。结果 ①MD组G1287A基因AA基因型与A等位基因频率高于对照组。②G1287A各等位基因及基因型OR值也具梯度升高的趋势,但未达到统计学意义(P>0.05)。③EPQ各纬度罹患MD风险的相对危险度OR及OR95%CI:危险变量EPQ-P为4.152(2.276,7.575)、EPQ-N为16.157(7.918,32.969),保护变量EPQ-E为0.093(0.048,0.181)。④利用Logistic多元回归方程计算控制人格对MD的发病风险后的调整OR值,抑郁障碍CC等位基因调整OR升高(由2.907上升到4.478)外;其他等位基因和基因型的调整OR均下降(OR范围0.745~1.338)。结论在控制人格对MD的发病风险后,在中国汉族人群中只有CC基因型可能是MD的危险因素。 相似文献
4.
Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is
relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D2-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality
disorder (ASPD), and nine healthy controls. Methods: [123I]PE2I and [123I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D2-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent
alcohol abuse.
Received: 22 March 1999 / Final version: 25 June 1999 相似文献
5.
Verhoeff NP 《Psychopharmacology》1999,147(3):217-249
This article will review the capabilities and accomplishments of radiotracer imaging with single photon emission computed
tomography (SPECT) and positron emission tomography (PET) to measure pre-, post-, and ”intra-synaptic” aspects of dopaminergic
(DAergic) neurotransmission. The presynaptic site can be labeled with probes for the dopamine transporter (DAT) or the synthetic
enzyme aromatic l-amino acid decarboxylase (”dopa decarboxylase”). The postsynaptic sites can be labeled with probes for either the dopamine
D1 receptor (D1R) or the dopamine D2 receptor (D2R). The ”synaptic” measurements are made indirectly by measurements of the interaction/displacement of receptor tracers by
endogenous dopamine (DA). Agents are used which either release (e.g., amphetamine) or deplete (e.g., alpha-methyl-paratyrosine
(AMPT), an inhibitor of tyrosine hydroxylase) tissue stores of DA. The application of these paradigms will be reviewed with
special emphasis to neuropsychiatric diseases such as schizophrenia and idiopathic Parkinson’s disease (IPD).
Received: 21 January 1999 / Accepted: 13 July 1999 相似文献
6.
Reneman L Booij J Lavalaye J de Bruin K Reitsma JB Gunning B den Heeten GJ van Den Brink W 《Psychopharmacology》2002,159(3):335-340
RATIONALE: Tablets sold as ecstasy often contain not only 3,4-methylenedioxymethamphetamine (MDMA) but other compounds well known to cause dopaminergic neurotoxicity, such as (meth)amphetamine. Furthermore, the use of ecstasy in the Netherlands is often combined with the use of amphetamine. However, little is known about the effects of ecstasy use or the combination of ecstasy and amphetamine use on dopamine (DA) neurones in the human brain. OBJECTIVES: This study was designed to investigate the effects of ecstasy as well as the combined use of ecstasy and amphetamine on the density of nigrostriatal DA neurones. METHODS: [123I]beta-CIT SPECT was used to quantify striatal DA transporters. Striatal [123I]beta-CIT binding ratios of control subjects ( n=15) were compared with binding ratios of ecstasy users ( n=29) and individuals with a history of combined ecstasy and amphetamine use ( n=9) after adjustment for age. RESULTS: Striatal [123I]beta-CIT binding ratios were significantly lower in combined ecstasy and amphetamine users compared to sole ecstasy users (6.75 versus 8.46, respectively: -20.2%, P=0.007). Binding ratios were significantly higher in ecstasy users when compared to controls (8.46 versus 7.47, respectively: +13.2%, P=0.045). CONCLUSIONS: These initial observations suggest that the sole use of ecstasy is not related to dopaminergic neurotoxicity in humans. In contrast, the reported use of amphetamine by regular users of ecstasy seems to be associated with a reduction in nigrostriatal DA neurones. 相似文献
7.
M. Iurlo M. Leone B. Schilström L. Linnér G. Nomikos P. Hertel B. Silvestrini T. Svensson 《Psychopharmacology》2001,159(1):98-104
In vivo microdialysis was used to investigate the effects of acute injections of harmine on extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxindoleacetic acid (5-HIAA) in the striatum of awake rats. Administration of harmine in doses of 0.5, 2.5, and 10 mg/kg (i.p.) elicited a dose-dependent increase of the dopamine efflux to 152, 173, and 243% and a decrease in DOPAC to 52, 36, and 10%, and HVA to 67, 45, and 20% throughout, respectively; 5-HIAA concentrations were decreased to 81, 74, and 72% only. In contrast to D-amphetamine, which also increases dopamine release and decreases its metabolites, the stimulatory action of harmine on dopamine release in the striatum was totally abolished in the presence of tetrodotoxin (1 microM). Similar to monoamine oxidase (MAO)-A inhibitors, harmine potentiated the stimulatory effect of D-amphetamine (10 microM), infused by reverse microdialysis in the striatum, on dopamine release. Pre-treatment with the benzodiazepine receptor antagonist flumazenil (5 mg/kg, i.p.) did not modulate the effect of harmine on striatal dopamine release and metabolism. Administration of the reversible MAO-A inhibitor, moclobemide (20 mg/kg, i.p.), induced an increase in dopamine to 256% and a decrease in DOPAC, HVA, and 5-HIAA to 30, 24, and 62%, respectively, reproducing a pattern similar to that of harmine. Taken together, these results indicate that harmine affects the brain dopamine system probably by acting as a MAO-A inhibitor and not as an inverse agonist for the benzodiazepine receptors. 相似文献
8.
Dopamine (DA) signaling in the central nervous system mediates the addictive capacities of multiple commonly abused substances, including cocaine, amphetamine, heroin and nicotine. The firing of DA neurons residing in the ventral tegmental area (VTA), and the release of DA by the projections of these neurons in the nucleus accumbens (NAc), is under tight control by cholinergic signaling mediated by nicotinic acetylcholine (ACh) receptors (nAChRs). The capacity for cholinergic signaling is dictated by the availability and activity of the presynaptic, high-affinity, choline transporter (CHT, SLC5A7) that acquires choline in an activity-dependent matter to sustain ACh synthesis. Here, we present evidence that a constitutive loss of CHT expression, mediated by genetic elimination of one copy of the Slc5a7 gene in mice (CHT+/−), leads to a significant reduction in basal extracellular DA levels in the NAc, as measured by in vivo microdialysis. Moreover, CHT heterozygosity results in blunted DA elevations following systemic nicotine or cocaine administration. These findings reinforce a critical role of ACh signaling capacity in both tonic and drug-modulated DA signaling and argue that genetically imposed reductions in CHT that lead to diminished DA signaling may lead to poor responses to reinforcing stimuli, possibly contributing to disorders linked to perturbed cholinergic signaling including depression and attention-deficit hyperactivity disorder (ADHD). 相似文献
9.
It was demonstrated that the influence of i.v. administered probenecid on HVA concentration in CSF was less pronounced in a group of retarded depression than in a group of non-retarded depression and a non-depressive control group. The figures corresponded to that found in Parkinson patients.These findings suggest a decreased consumption of dopamine in the brain in retarded depression. This might be understood as an indication that, disorders of cerebral dopamine metabolism are related not so much to a specific nosological entity as to a given motor status, possibly that of hypokinesia.This study was supported by grants from the Netherlands Organization for Pure Research (Z.W.O.). 相似文献
10.
Theunissen EL van Kroonenburgh MJ van Deursen JA Blom-Coenjaerts C Ramaekers JG 《Psychopharmacology》2006,187(1):95-102
Rationale First- and second-generation antihistamines are known to produce different degrees of sedation. However, a few studies have shown that the H1-antagonist fexofenadine produces mild stimulating effects. One hypothesis suggests that this is due to fexofenadine producing an increase in dopamine levels by blocking the dopamine transporter.Objective In this study, it was investigated whether a high dose of fexofenadine blocks the dopamine transporter in the striatum. In addition, the effect of fexofenadine on cognitive performance and motor impulsivity was investigated.Methods Sixteen healthy subjects were given either placebo or fexofenadine 360 mg. The binding potential of N-w-fluoropropyl-2β-carbomethoxy-3β-[4-iodophenyl] nortropane ([123I]FP-CIT) was measured using single-photon emission computed tomography (SPECT). Cognitive performance was measured in 40 subjects (20 placebo, 20 fexofenadine) using a digit symbol substitution test (DSST) and a stop signal task. In addition, subjective and physiological effects of fexofenadine were observed.Results The SPECT data demonstrated that there was no difference in the binding potential of FP-CIT at the dopamine transporter in the striatum between the placebo- and fexofenadine-treated subjects. The behavioral results showed that fexofenadine improved performance on the DSST at T
max of the drug. Fexofenadine did not affect motor impulsivity, subjective experience, or physiological measures.Conclusion No evidence was provided to support the hypothesis that fexofenadine stimulates performance by blocking the dopamine transporter. The behavioral data suggest that a high dose of fexofenadine can stimulate performance in cognitive tasks. 相似文献
11.
Multiple, rare, human dopamine (DA) transporter (hDAT, SLC6A3) coding variants have been described, though to date they have been incompletely characterized. Here we present studies analyzing the function and regulation of five naturally occurring coding variants, V55A, R237Q, V382A, A559V and E602G, expressed in COS-7 and SH-SY5Y cells. All variants, except V382A, exhibited levels of surface protein expression and DA transport activity comparable to hDAT. V382A, divergent at the most highly conserved residue among reported hDAT variants, exhibited significantly diminished surface expression, likely derived from inefficient plasma membrane delivery. Moreover, a greater expression of V382A protein was required to achieve comparable levels of transport to hDAT, consistent with a loss of transport function. V382A displayed a decrease in sensitivity to phorbol ester (PMA)-induced internalization, as well as an altered substrate selectivity for DA versus norepinephrine (NE). Analysis of PMA-induced V382A internalization revealed a trafficking-independent action of PMA, consistent with the existence of a surface-localized, transport-inactive state. 相似文献
12.
Meyer JH Goulding VS Wilson AA Hussey D Christensen BK Houle S 《Psychopharmacology》2002,163(1):102-105
RATIONALE: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design. RESULTS: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion. 相似文献
13.
Rapid delivery of the dopamine transporter to the plasmalemmal membrane upon amphetamine stimulation 总被引:1,自引:0,他引:1
The dopamine transporter, DAT, is a primary regulator of dopamine (DA) signaling at the synapse. Persistent stimulation with the substrate amphetamine (AMPH) promotes DAT internalization. AMPH rapidly elicits DA efflux, yet its effect on DAT trafficking at short times is unknown. We examined the rapid effect of AMPH on DAT trafficking in rat striatal synaptosomes using biotinylation to label surface DAT. Within 30s of treatment with 3 microM AMPH, synaptosomal DAT surface expression increased to 163% of control and remained elevated through at least 1 min before returning to control levels at 2.5 min. The increase in surface DAT was cocaine-sensitive but was not produced by DA itself. A 1-min preincubation with AMPH did not alter [(3)H]DA uptake, but did result in a higher basal DA efflux and efflux elicited in the presence of AMPH as compared to vehicle pretreatment. Reversible biotinylation experiments demonstrated that the AMPH-stimulated rise in surface DAT is due to an increase in the delivery of DAT to the plasmalemmal membrane rather than a reduction of the endocytic process. These studies suggest that AMPH has a biphasic effect on DAT trafficking and acts rapidly to regulate DAT in the plasmalemmal membrane. 相似文献
14.
Relationships among dopamine transporter affinities and cocaine-like discriminative-stimulus effects
Rationale: The discriminative-stimulus effects of cocaine have been reported to be mediated by indirect agonist actions initiated by
the blockade of dopamine uptake, and the potencies of drugs that have discriminative-stimulus effects like cocaine are directly
related to their dopamine transporter binding affinities. The binding to the dopamine transporter by cocaine and many of its
analogs has been reported to fit better using a two-site model than a one-site model. Objectives: The present study examined the relationship among binding affinities of dopamine uptake inhibitors at these two sites and
their potencies to produce discriminative-stimulus effects. Methods: The inhibition constants (K
i values) were derived for unlabeled dopamine uptake inhibitors for displacement of [3H]WIN 35,428 from rat caudate putamen membranes. These K
i values were related to the ED50 values obtained in rats trained to discriminate 10 mg/kg cocaine from saline injections under a fixed-ratio 20 schedule of
food reinforcement. Results: Among the dopamine uptake inhibitors studied, the binding data for eight compounds (WIN 35,428, nomifensine, WIN 35,981,
WIN 35,065-2, methylphenidate, cocaine, cocaethylene, and bupropion) were better fit by a two-site model than a one-site model.
The data for the remaining eleven compounds (RTI-31, RTI-55, RTI-121, RTI-32, LU19-005, BTCP, GBR12909, GBR12935, mazindol,
LU17-133, and EXP561) were better fit by a one-site model. Of the drugs that were fit best by a two-site model, there was
a higher correlation among the K
i values for the high-affinity site and the ED50 values (R2=0.655; P=0.015) than there was for the low-affinity site (R2=0.543; P=0.037). Of the remaining drugs, there was a high correlation among the K
i values and the ED50 values for the discriminative-stimulus effects (R2=0.523; P=0.012). Conclusions: These data suggest that the discriminative-stimulus effects of cocaine are more closely related to actions mediated by high-affinity
binding to the dopamine transporter than they are to actions mediated by the low-affinity site. The further assessment of
the respective contributions of high- and low-affinity binding to the behavioral effects of cocaine will be greatly enhanced
with the development of pharmacological tools that have a high degree of selectivity for one of these components.
Received: 24 May 1999 / Final version: 30 July 1999 相似文献
15.
The activity of the presynaptic dopamine (DA) transporter (DAT) is critical in mediating the magnitude and duration of dopaminergic signaling in the brain. Multiple genetic studies have found an association between attention deficit hyperactivity disorder (ADHD) and a variable number tandem repeat (VNTR) in the 3'-untranslated region (3'VNTR) of the hDAT gene (SLC6A3), however none of these studies examined the hDAT coding region for polymorphisms. Thus, we sought evidence of polymorphisms in hDAT, focusing on the coding region and splice junctions, utilizing genomic DNA from children diagnosed with ADHD. Two separate ADHD cohorts (N=70 and N=42) were screened and sampled for both status of the 3'VNTR and for common/novel genomic variants. We found evidence of increased DAT variation in African-American subjects as well as in predominantely hyperactive-impulsive probands. Cumulatively, multiple hDAT sequence variants were identified, including five novel variants, as well as one nonsynonymous single nucleotide polymorphism (SNP), converting Ala559 to Val (A559V). A559V was identified in two Caucasian male siblings with ADHD and both subjects were homozygous for the ADHD-associated, 10-repeat 3'VNTR allele. Interestingly, the A559V variant was previously identified in a subject with bipolar disorder [. Molecular Psychiatry 5, 275], a psychiatric disorder that has a significant number of overlapping symptoms with ADHD. 相似文献
16.
Mateos JJ Lomeña F Parellada E Mireia F Fernandez-Egea E Pavia J Prats A Pons F Bernardo M 《Psychopharmacology》2007,191(3):805-811
Introduction
Drug induced parkinsonism (DIP) is directly related to dopamine D2 receptor blockade. However, there are many references describing parkinsonian signs (PS) in naive-patients. In our previous study, we observed lower DAT binding in a group of first-episode schizophrenic patients after short-term treatment with risperidone, compared with age-matched healthy controls.Aim
To clarify if DAT decrease could be an illness trait, excluding the effect of antipsychotics on DAT availability, and to determine whether DAT availability before treatment with antipsychotics may predict subsequent development of PS.Materials and methods
A new series of 20 neuroleptic-naive schizophrenic patients and 15 healthy subjects was recruited. SPECT with [123I] FP-CIT (DaTSCAN®) was performed before starting antipsychotics and after 4 weeks of treatment. PS and psychopathological status were assessed by the Simpson–Angus (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using ROIs placed in the caudate, putamen and occipital cortex.Results
Schizophrenic patients showed lower DAT binding compared with the healthy subjects at baseline (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight schizophrenic patients of the DIP group were symptomatic for PS at baseline, in comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at endpoint (p=0.984). Finally, no differences between baseline–endpoint DAT binding were observed, neither in the DIP group (p=0.767) nor in the NoDIP group (p=0.093).Conclusion
Our new series of first-episode naive-schizophrenic patients (1) points out DAT dysfunction as an illness trait due to the significantly lower DAT binding in schizophrenic patients in comparison to healthy subjects; (2) supports the results of other authors who describe PS in never-treated patients; (3) confirms that [123I] FP-CIT does not allow us to predict which patients will develop parkinsonism due to the lack of differences between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics on DAT due to the lack of differences in [123I] FP-CIT before and after a 4-week-treatment period.17.
Lomeña F Catafau AM Parellada E Bernardo M Font M Gutiérrez F Pavía J 《Psychopharmacology》2004,172(2):165-169
Most post-mortem autoradiographic studies have described striatal dopamine D2 receptor up-regulation due to chronic neuroleptic exposure. The aim of our study was to compare in-vivo striatal D2 receptor density in neuroleptic-naive and neuroleptic-free schizophrenic patients. We included 28 young (mean age: 28±8 years) acute psychotic patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder. Enrolled patients were either first-episode neuroleptic-naive (n=12) or neuroleptic-free (n=16) after a minimum washout period of 7 days. All neuroleptic-free subjects had previously received neuroleptic treatment for a median period of 3.5 years. Both groups were evaluated using standard clinical scales. In-vivo striatal D2 receptor binding was assessed by basal ganglia/frontal cortex ratios using 123I-IBZM SPECT. No statistically significant differences were found in age or clinical assessment between neuroleptic-naive and neuroleptic-free schizophrenic patients. No differences were found in the basal ganglia/frontal cortex ratios of neuroleptic-naive (1.78±0.11) and neuroleptic-free (1.81±0.15) patients. No striatal uptake laterality was observed in either group. No correlation was demonstrated between BG/FC ratios and duration of illness, period of neuroleptic exposure or time of drug washout. We conclude that our neuroleptic-naive and neuroleptic-free schizophrenic patients did not show differences in striatal D2 receptor binding, suggesting that IBZM-SPECT fails to detect D2 receptor up-regulation induced by chronic exposure to neuroleptic drugs. 相似文献
18.
Jyrki T. Kuikka Liisa Tammela Leila Karhunen Aila Rissanen Kim A. Bergström Hannu Naukkarinen Esko Vanninen Jari Karhu Raimo Lappalainen Eila Repo-Tiihonen Jari Tiihonen Matti Uusitupa 《Psychopharmacology》2001,155(3):310-314
RATIONALE: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. OBJECTIVE: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. METHODS: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-beta-CIT, which specifically labels 5-HT transporters. RESULTS: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1 +/- 0.5 versus 2.9 +/- 0.5, respectively). CONCLUSIONS: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women. 相似文献
19.
Best SE Sarrel PM Malison RT Laruelle M Zoghbi SS Baldwin RM Seibyl JP Innis RB van Dyck CH 《Psychopharmacology》2005,183(2):181-189
Objectives The effect of gender and female menstrual cycle on human striatal dopamine transporters (DATs) was investigated with single-photon emission computed tomography (SPECT) using the ligand 2β-carbomethoxy-3β-(4-[123I]iodophenyl)tropane.Methods Ten female subjects aged 18–40 years (25.3±7.3 years) were scanned twice during the early follicular and the mid-luteal phases to detect any hormone-mediated changes in DAT availability in the striatum or serotonin transporter (SERT) availability in brainstem–diencephalon. Plasma estradiol and progesterone levels were obtained at the time of SPECT and confirmed the expected increases from the follicular to the luteal phases. Finally, in a post hoc analysis of a previously published healthy-subject sample, striatal DAT availability was compared between 70 male and 52 female subjects who ranged in age from 18 to 88 years.Results In the ten menstrual cycle subjects, DAT availability (V3″) in striatum and SERT availability in brainstem–diencephalon did not differ between follicular and luteal phases. Moreover, change in V3″ for striatum or brainstem–diencephalon was uncorrelated with change in plasma estradiol or progesterone from the follicular to the luteal phase. In the larger healthy-subject sample, there was no significant effect of gender or the interaction of age and gender on striatal V3″.Conclusions These findings suggest that in using DAT or SERT ligands in the study of neuropsychiatric disorders, matching of female subjects according to a menstrual cycle phase is unnecessary. Although the present investigation did not confirm previous reports of gender differences in striatal DAT availability, controlling for gender in such studies still seems advisable. 相似文献
20.
Neurosteroids in depression: a review 总被引:3,自引:3,他引:0
Abstract
Rationale. A deregulation in concentrations of the neurosteroids (allo)pregnanolone and 3α,5α-tetrahydrodeoxycorticosterone (3α,5α-TH
DOC) has been found in depressed patients. These levels normalize following treatment with selective serotonin reuptake inhibitors
(SSRIs). Furthermore, administration of the neurosteroid dehydroepiandrosterone (DHEA) to depressed patients is associated
with an improvement in the symptoms of depression.
Objective. The aim of the present review is to clarify the mechanisms whereby neurosteroids, particularly allopregnanolone and DHEA,
are involved in depression and to discuss the effect of SSRIs on allopregnanolone concentration.
Methods. Literature on preclinical and clinical research has been analyzed in relation to the pathophysiology of depression.
Results. Decreased plasma and cerebrospinal fluid concentrations of allopregnanolone in depressed patients increase to normal levels
following effective psychopharmacological treatment. This might either be a physiological aspect of improvement in the symptoms
of depression or a pharmacologically induced alteration. Several findings support the hypothesis of an antidepressant effect
of allopregnanolone. These include an antidepressant effect demonstrated in an animal model of depression and a suppressing
effect on corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) gene expression. SSRIs increase levels of allopregnanolone,
but this effect is not confined to this class of drugs alone. The beneficial effect of DHEA administration in depressed patients
might result from its sigma 1 receptor-mediated enhancement of noradrenaline and serotonin neurotransmission, antiglucocorticoid
effects, and cognition enhancing effects.
Conclusions. Indirect genomic (allopregnanolone) and non-genomic (allopregnanolone and DHEA) mechanisms are involved in the neurosteroidogenic
pathophysiology of depression. Clinical studies in homogeneous groups of non-pharmacologically treated depressed patients
are required to elucidate this relationship further.
Electronic Publication 相似文献