The repressing effect of fenoldopam on the development of thoracic aortic aneurysm in mice / 安徽医科大学学报

Objective @#To investigate whether fenoldopam (FNDP) ( an agonist of type 1 dopamine receptor) has a protective effect on thoracic aortic aneurysm ( TAA) in mice .@*Methods @#Three-week-old male C57BL/6J mice were treated with β-aminopropionitrile (BAPN) to induce TAA . The mice were divided into three groups : the con- trol group , the BAPN group , and the BAPN + FNDP group (FNDP inj ected intraperitoneally) . The incidence and survival rate of TAA were recorded . Gross anatomy of the whole aortae was ob served . Elastin staining was per- formed to assess morphological change , while immunohistochemistry was employed to evaluate the expressions of matrix metalloproteinase 2(MMP2) , matrix metalloproteinase 9( MMP9) and cluster of differentiation 68( CD68) respectively. Gelatin zymography was conducted to assess MMP2 and MMP9 activity. Reverse transcription-poly- merase chain reaction (RT-PCR) was performed to measure the mRNA expression levels of dopamine receptor D1(D1DR) , dopamine receptor d2 (D2DR) , dopamine receptor d3 (D3DR) , dopamine receptor d5 (D5DR) , in- terleukin-1β(IL-1β) , interleukin-6 (IL-6) , tumour necrosis factor-α (TNF-α) , monocyte chemoattractant pro- tein-1 (MCP-1) , alpha-smooth muscle actin ( α-SMA) and smooth muscle protein 22 -alpha (SM22α) .@*Results@#Compared to the control group , the BAPN group exhibited significant formation of TAA . Elastic fiber disruption was also ob served in the thoracic aortic wall , along with a significant decrease in the mRNA levels of D1DR and D5DR. The BAPN + FNDP group showed a significant reduction in the incidence of TAA formation and the rate of aneu- rysm rupture compared to the BAPN group . The disruption and rupture of elastic fibers in the thoracic aortic wall were significantly improved in the BAPN + FNDP group . The levels of MMP2 and MMP9 in the thoracic aortic wall significantly decreased , and the enzymatic activity of MMP2 in the serum was significantly reduced . Moreover , macrophage infiltration in the thoracic aortic wall was significantly reduced and the mRNA levels of IL-1β, IL-6 , TNF-αand MCP-1 also significantly decreased after FNDP treatment. There was no statistically significant differ- ence in the mRNA levels of α-SMA and SM22α.@*Conclusion @#FNDP shows an inhibitory effect on TAA progres- sion in mice , suggesting a potential of FNDP as a therapeutic agent for TAA .

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience

ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

Comparative assessment of effect of malt with different bud length on prolactin in hyperprolactinemia rat

Malt is the mature fruit of Hordeum vulgare L. after germination and drying and has been applied for treatment female abnormal galactorrhea. Previous studies have showed total alkaloids in malt have anti-HPRL effect. However, total alkaloids of malt change with the growth cycle, and the specified levels of total alkaloids in different bud length of malt have not been decided. To determine the definitive level of total alkaloids in different buds of malt and the most suitable bud length for clinical application by comparing effects on hyperprolactinemia rat. During the budding of malt, the content of total alkaloids first increased and then decreased, and it peaked at a bud length of 0.75 cm. Treated the HPRL model rats with different buds of malt, the PRL level was decreased, the number of PRLpositive cells and the mRNA expression level in the pituitary were significantly declined, and the number of dopamine D1 and D2 receptors in the hypothalamus was increased. The above changes were most significant in 0.75 cm bud. These results suggest that in terms of the content of effective substance and the effects on HPRL model rats, a malt bud length of 0.75 cm is optimal for clinical application.

Effect of dopamine and its receptors on the development of visual deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#Myopic population of China is already nearly 600 million, the rate of teenager myopic occupies the first place in the world, myopia hsa already became one of the main diseases that endangers our adolescent's health. Dopamine is the main catecholamine in retina. Many studies have found that increasing the content of dopamine can effectively inhibit the development of myopia. Form-deprivation myopia is a classical method of myopia modeling. By observing the influence of dopamine and its receptors on the development of form-deprivation myopia, its role in the development of myopia can be reflected, and it is of great significance to guide and control the occurrence and development of myopia. In this paper, the effects of dopamine and its receptors on the development of form-deprivation myopia were reviewed in order to provide reference for the prevention and treatment of myopia.

Early-Life Stress in D2 Heterozygous Mice Promotes Autistic-like Behaviors through the Downregulation of the BDNF-TrkB Pathway in the Dorsal Striatum

A number of specific genetic variants including gene mutations and single nucleotide variations have been identified in genomewide association studies of autism spectrum disorder (ASD). ASD phenotypes in individuals carrying specific genetic variations are manifest mostly in a heterozygous state. Furthermore, individuals with most genetic variants show incomplete penetrance and phenotypic variability, suggesting that non-genetic factors are also involved in developing ASD. However, the mechanisms of how genetic and environmental factors interactively promote ASD are not clearly understood. In the present study, we investigated whether early-life stress (ELS) in D2 dopamine receptor heterozygous knockout (D2(+/−)) mice induces ASD-like symptoms. To address that, we exposed D2 heterozygous pups to maternal separation stress for 3 h daily for 13 days beginning on postnatal day 2. D2(+/−) adult mice that had experienced ELS exhibited impaired sociability in the three-chamber test and home-cage social interaction test and increased grooming behavior, whereas wildtype littermates exposed to ELS did not show those phenotypes. ELS-exposed D2(+/−) mice had decreased levels of BDNF, TrkB, phospho-ERK1/2 and phospho-CREB in the dorsal striatum. Administration of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) to ELS-exposed D2(+/−) mice rescued the sociability deficits and repetitive behavior. In contrast, behavioral rescue by 7,8-DHF in ELS-exposed D2(+/−) mice was blocked when TrkB expression in the dorsal striatum was locally inhibited by the injection of TrkB-siRNA. Together, our results suggest that the interaction between ELS and defective D2 gene function promotes autistic-like behaviors by downregulating the BDNF-TrkB pathway in the dorsal striatum.

A Functional Polymorphism in the DRD1 Gene, That Modulates Its Regulation by miR-504, Is Associated with Depressive Symptoms

OBJECTIVE: The aim of this study was to examine a possible association between depressive symptoms and a functional polymorphism (rs686) that modulates the regulation of DRD1 gene by miR-504. METHODS: A total of 239 young Colombian subjects were evaluated with the Patient Health Questionnaire-9 (PHQ-9) scale and genotyped for the rs686 polymorphism. A linear regression model, corrected by age and gender, was used. RESULTS: A significant association between the rs686 polymorphism and PHQ-9 scores was found, under a dominant genetic model (p=0.0094). CONCLUSION: These results provide novel evidence about the growing role of inherited variants in binding sites for brain-expressed miRNAs on depressive symptomatology.

Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

Dopamine receptors gene expression in male rat hippocampus after administration of MDMA (ecstasy) / La expresión génica de receptores de dopamina en el hipocampo de ratas macho después de la administración de MDMA (éxtasis)

Ecstasy is one of the most popular amusing drugs among young people. Documents indicate some effects of Ecstasy on hippocampus and close relations between dopaminergic functions with reward learning. Therefore, the aim of this study was evaluation of the chronic effects of Ecstasy on memory in male Wistar rats and determination of dopamine receptors' gene expression in hippocampus. Forty adult male Wistar rats randomly distributed in five groups: Control, sham (received 1 ml/kg 0.9% saline) and three experimental groups were: Exp. 1 (2.5 mg/kg), Exp. 2 (5 mg/kg), and Exp. 3 (10 mg/kg) received MDMA intraperitoneally once every 7 days (3 times a day, 3 hours apart) for 4 weeks. Before the first injection animals trained in Shuttle Box memory and tested after the last injection. 24 hours after the final testing, brains of rats were dissected and hippocampus was removed and homogenized. After total RNA extraction and cDNA synthesis, expression of dopamine receptor genes in the hippocampus determined with Real-Time PCR. Our results showed that 2.5 and 5 mg/kg MDMA-treated groups had memory impairment. Also we found that MDMA increased the mRNA expression of dopamine receptors in hippocampus and the highest increase found in dopamine D1 receptors in the 5 mg/kg experimental group. We concluded that low doses of Ecstasy could increase Dopamine takers gene expression in hippocampus and disorder avoidance memory. But in high doses the increase in Dopamine takers gene expression was not as much as that in low doses and avoidance memory disorder was not observed.

El éxtasis es una de las drogas de diversión más populares entre los jóvenes. La investigación reporta algunos de los efectos del éxtasis sobre el hipocampo y la relación entre las funciones dopaminérgicas con la recompensa en el aprendizaje. El objetivo de este estudio fue la evaluación de los efectos crónicos del éxtasis en la memoria de ratas macho Wistar y la determinación de la expresión de genes receptores de dopamina en el hipocampo. Cuarenta ratas macho adultas fueron distribuidas al azar en cinco grupos: grupo control, simulado (a 1 ml/kg 0,9% de solución salina) y tres grupos experimentales: Grupo exp. 1 (2,5 mg/kg), Exp. 2 (5 mg/kg), y Exp. 3 (10 mg/kg) recibió MDMA vía intraperitoneal cada 7 días (3 veces al día, con 3 horas de diferencia) durante 4 semanas. Antes de la primera inyección los animales fueron entrenados en memoria Shuttle Box y examinados después de la última inyección. Veinticuatro horas después de la prueba final, los cerebros de las ratas fueron diseccionados, el hipocampo fue separado y homogeneizado. Después de la extracción total de ARN y síntesis de ADNc, la expresión de genes de los receptores de dopamina en el hipocampo fue determinado con PCR en tiempo real. Nuestros resultados mostraron que los grupos de 2,5 kg y 5 mg/MDMA tratados tenían deterioro de la memoria. Además, encontramos que la MDMA aumentó la expresión de ARNm de los receptores de dopamina en el hipocampo y el aumento mayor se observó en los receptores D1 de dopamina en el 5 mg/kg Grupo experimental. En conclusión, las dosis bajas de éxtasis podrían aumentar tomadores de expresión génica de la dopamina en el hipocampo y trastornos de la memoria. Sin embargo, en dosis altas el aumento de la expresión génica no mostró un aumento significativo, a diferencia de los resultados con dosis bajas, tampoco se observaron trastornos disociativos de memoria.

Predominant D1 Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration

The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3rd day. CART peptides were over-expressed on the 5th day in the striata of behaviorally sensitized mice. A higher proportion of CART+ cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D1R and D2R antagonists, SCH 23390 (D1R selective) and raclopride (D2R selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D1R and D2R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the D1R-KO mice, but not in the D2R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D1R.

Trial of Metoclopramide on Oro-facial Dyskinesia Following Traumatic Brain Injury: A Case Report

Oro-facial dyskinesia is characterized by involuntary repetitive movements of the tongue, lip, or jaw, which is known to be derived by variable causes. Pre- and post-synaptic dopamine receptor abnormalities by degenerative changes in the brain seem to be the key pathophysiology, but the exact mechanism still remained to be unknown. Metoclopramide can pass the blood-brain barrier, which is known for a selective presynaptic autoregulating dopamine D2 receptor antagonist in the brain, and is usually prescribed for dyspepsia, nausea and vomiting. In particular, it was also reported to improve the symptoms of diurnal bruxism after brain injury. With reviewing some of literatures, we present a case of 27 year old man with traumatic brain injury who showed improvement of oro-facial dyskinesia after taking oral metoclopramide.

Impact of COMT H108L, MAOB int 13 A>G and DRD2 haplotype on the susceptibility to Parkinson’s Disease in South Indian subjects.

In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson’s disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.

Effects of benzodiazepine and ivermectin on Girardiatigrina (Platyhelminthes: Turbellaria) / Efeitos de benzodiazepínico e ivermectina em Girardia tigrina (Platyhelminthes: turbellaria)

Four hundred specimens of Girardia (=Dugesia) tigrina separated in groups of 5 were subjected to concentrations of 10, 25 and 50 ppm diazepam (DZP) and 1, 5 and 10 ppm of ivermectin (IVM), substances with actions associated with ionophore chlorine and GABA receptors in neuromuscular endings in various animals. The period of turbellarians exposure at different concentrations used was 3 h, for DZP while those to IVM were 30, 60, 120 minutes, 12 and 24 h for each tested concentration. In groups exposed to DZP hyperkinetic and type "C" and screw like movements were observed in all concentrations. However, at concentrations of 50 and 25 ppm, the pharynx was protruded in 100% of the specimens followed by detachment at concentration of 50 ppm and 60% at a concentration of 25 ppm. Mortality reached 100% 24 hours after exposure to a concentration of 50 ppm and 30% of planarians became degenerated at a concentration of 25 ppm. Planarians submitted to concentrations of 10 and 25 ppm remained alive and without hyperkinetic movements 48 hours after exposure. In IVM exposed groups, hyperkinetic and contractile movements were observed as well as type "C" screw like movements in all tested concentrations and time dependent. The group exposed for 24 hours showed a time dependent variation in mortality from 0 to 100%. The turbellarians were alive for 48 hours in 1 ppm during 12 hours of exposure but with 24 hours of exposure the mortality reaches 20%. The data indicate a time and concentration dependent relationship in the mode of action of these drugs.

Quatrocentos exemplares de Girardia (=Dugesia) tigrina separados em grupos de 5 foram submetidos a concentrações de 10, 25 e 50ppm de diazepam (DZP) e 1, 5 e 10ppm de ivermectina (IVM), substâncias com ações associadas ao ionóforo cloro e receptores GABA em terminações neuromusculares em vários animais. O tempo de exposição dos turbelários às diferentes concentrações utilizadas de DZP foi de 3 horas, enquanto para cada concentração de IVM os exemplares permaneceram expostos durante 30, 60, 120 minutos, 12 e 24 horas. Nos grupos expostos ao DZP foram verificados movimentos hipercinéticos tipo parafuso e tipo "C" e exposição da faringe ao exterior em todas as concentrações. Houve perda da faringe em 90% dos espécimes na concentração de 50ppm e 60% em 25ppm. Foi verificado também 100% de mortalidade após 24 horas em concentração de 50ppm e 30% de degeneração dos platyhelminthes na concentração de 25ppm. No exame realizado 48 horas após a exposição, as planárias submetidas às concentrações de 25 e 10 ppm permaneceram vivas e não mais apresentaram movimentos hipercinéticos. Nos grupos expostos à IVM, foram observados movimentos contráteis e movimentos hipercinéticos tipo parafuso e tipo "C" em todas as concentrações e foi dependente do tempo de exposição. O percentual de mortalidade variou de 0 a 100 nas primeiras 24 horas de observação também dependente do tempo de exposição. Em concentração de 1 ppm e até 12 horas de exposição não foi observada mortalidade dos animais até 48 horas após. Entretanto com 24 horas de exposição e exame 24 horas após a mortalidade chega a 20% dos exemplares persistindo até o final do período de observação. Os dados indicam uma relação dependente da concentração e do tempo no modo de ação destas substâncias.

Trial of Oral Metoclopramide on Diurnal Bruxism of Brain Injury

Bruxism is a diurnal or nocturnal parafunctional activity that includes tooth clenching, bracing, gnashing, and grinding. The dopaminergic system seems to be the key pathophysiology of bruxism and diminution of dopaminergic transmission at the prefrontal cortex seems to induce it. We report two patients with diurnal bruxism in whom a bilateral frontal lobe injury resulted from hemorrhagic stroke or traumatic brain injury. These patients' bruxism was refractory to bromocriptine but responded to low-dose metoclopramide therapy. We propose that administering low doses of metoclopramide is possibly a sound method for treating bruxism in a brain injury patient with frontal lobe hypoperfusion on positron emission tomography imaging.

Quantitative Autoradiographic Study on Receptor Regulation in the Basal Ganglia in Rat Model of Levodopa-induced Motor Complications / 华中科技大学学报（医学）（英德文版）

In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications,quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2,N-methyl-D-aspartate (NMDA),amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) and amino butyric acid (GABA) in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed.The rats were randomly assigned to three groups:normal,denervated and treatment-complicated groups.The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement (AIM) score was progressively increased during the course of levodopa treatment.Chronic treatment augmented DI receptors more than denervation,and reduced D2 receptors that were also increased by dopamine denervation.Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group.Levodopa treatment did not change receptors of nigral AMPA,pailidai GABA,and subthalamic GABA,which remained the same as that in denervation group.However,chronic treatment reversed the increase ofnigral GABA receptors caused by the lesion.It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson's patients.These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways,which is associated with levodopa-induced motor complications.

YKP1447, A Novel Potential Atypical Antipsychotic Agent

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT2A, Ki=0.61 nM, 5-HT2C, Ki=20.7 nM) and dopamine (D2, Ki=45.9 nM, D3, Ki=42.1 nM) receptors with over 10~100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED50=0.93 mg/kg) and DOI-induced head twitch (ED50=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED50=0.54 mg/kg) and the avoidance response (ED50=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED50=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

The Relationship between the Antipsychotics-Induced Weight Gain and the Dopamine D2, D3, and D4 Receptor Gene Polymorphisms in Korean Schizophrenic Patients / 대한정신약물학회지

OBJECTIVE: Excessive weight gain is often observed during chronic administration of antipsychotic drugs. Several lines of evidences implicate an important role for the dopamine D2 receptor in the regulation of food intake and energy metabolism. Therefore, we investigated the relationship between the antipsychotics-induced weight gain and the polymorphisms in the dopamine D2, D3, and D4 receptor genes (DRD2, DRD33, and DRD4, respectively). METHODS: We conducted a retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia (DSM-IV) treated with various antipsychotics (94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, weight gainers (weight gain=5%) and non-gainers (weight gain <5%) by percentile change of body weight at discharge compared to body weight at admission. We investigated the differences of the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4 between weight gainers and non-gainers. RESULTS: Among the 200 total patients of 200, 73 (36.5%) were categorized as weight gainers. There were no significant differences were observed in the frequencies of DRD2 and DRD4 alleles and genotypes between the weight gainers and non-gainers. However, the weight gainers were associated with carriers of the Gly allele (versus Ser allele) in the Ser9Gly polymorphism of the DRD3 (OR=1.699; 95% CI=1.075~-2.686; p=0.023) and associated with carriers of the Gly/Gly genotype (versus the Ser/Ser genotype) in the Ser9Gly polymorphism of the DRD3 (OR=3.328; 95% CI=1.305~-8.488; p=0.012). CONCLUSION: These results suggest that the Ser9Gly polymorphism of thein DRD3 may have an effect on the mechanism of antipsychotics-induced weight gain in patients with schizophrenia. Further research are needed to replicate these results.

The Relationship between the Therapeutic Response to Antipsychotic Drugs and the Dopamine D2, D3, and D4 Receptor Gene Polymorphisms in Korean Schizophrenic Patients

OBJECTIVES: A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to anti-psychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). METHODS: We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. RESULTS: Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. CONCLUSION: These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.

Roles of Dopamine in Proliferation of Gastric-Cancer Cells

PURPOSE: Dopamine is a neurotransmitter, but in the GIT, the roles of dopamine are a regulator of epithelial cell proliferation, an endogenous protective factor, and a regulator of stomach cancer cell proliferation. By using two different gastric-cancer cell lines, we assessed the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells. MATERIALS AND METHODS: To assess the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells, we investigated cell proliferation and the expression of D1, D2L, and D2S receptor in two gastric-cancer cell lines, SNU 601 and KCU-C2. The effects of dopamine and dopamine receptors on the level of the cell proliferation were determined by staining with an A/H/E (acridine orange, hoechst and ethidium bromide) mixture. RESULTS: After dopamine treatment, the cell viability was significantly decreased in SNU 601 cells (P<0.05) where the D2L receptor was absent, but not in KCU-C2 cells. After treatment with raclopride, a D2 receptor antagonist, dopamine-dose-dependent inhibition of cell proliferation was observed in SNU 601 cells (P<0.05). After treatment with SCH 23390, a D1 receptor antagonist, dopamine significantly increased cell proliferation in KCU-C2 cells (P<0.05), but inhibited cell proliferation in SNU 601 cells (no D2L receptor). CONCLUSION: The dopamine signal via the D1 or the D2S receptor inhibited proliferation of gastric-cancer cells, but that via the D2L receptor increased proliferation. These results suggest that the regulatory effects of dopamine in the gastric-cancer cell proliferation may be controlled by using dopamine receptors.

Down-regulation of Dopamine D1 Receptor in Rat Penile Tissue after Cavernous Neurotomy / 대한비뇨기과학회지

PURPOSE: Dopamine plays a critical role in promoting sexual drive and penile erection through dopamine receptors. This study was performed to investigate whether the cavernousal nerve controls the expression of peripheral dopamine D1 receptors in rat penile tissues after cavernousal nerve injury. MATERIALS AND METHODS: Male rats (n=20) were divided into two groups: a control group consisting of sham-operated rats (n=10) and an experimental group consisting of rats that underwent incision of the bilateral cavernous nerve (n=10). Three months later, the intracavernous pressure response was monitored using an intracavernous papaverine injection of 300 microgram. The expression of dopamine D1 receptor mRNA were studied using an RT-PCR method, and dopamine D1 receptor protein expression by Western blot analysis and immuno-histochemical staining in each group. The expressed band density of the RT-PCR and Western blot were measured by a densitometer. RESULTS: Erectile functions, as studied by intracavernosal papaverine injection at three months, were similar in both groups. The dopamine D1 receptor mRNA and protein expressions were significantly lower in the neurotomy group. The immuno-histochemical staining also showed a reduction in the dopamine D1 receptor expression in the neurotomy group compared with the control group. CONCLUSIONS: Our results show that dopamine D1 receptors in penile tissues were down-regulated following cavernousal nerve injury. These findings suggest that cavernousal nerve injury affects directly the reduction of dopamine D1 receptor expression, and that the action of dopamine on the cavernousal dopamine receptor will be affected in cavernousal nerve injured rats.