Comparison of unilateral medial forebrain bundle and unilateral striatum lesioned by 6-hydroxydopamine at early lesioned stage in rat model / 安徽医科大学学报

Objective@#To compare the functional changes of neurotransmitters in the dopamine ( DA) system of rats lesioned by 6-hydroxydopamine in unilateral medial forebrain bundle ( MFB) and unilateral striatum after 4 weeks of modeling．@*Methods @#Adult male Sprague-Dawley rats (n = 62) were divided randomly into four groups : single-site model ( one site striatal lesion model，n = 18) ，four-site model ( four sites striatal lesion model，n = 18) ，MFB model (MFB lesion model，n = 18) and a sham operated control group (n = 8) ．Immunohistochemical tyrosine hydroxylase (TH) staining was used to calculate the loss rate of positive DA neurons．The functional changes of dopamine transporters(DAT) and D2 receptors in rat models of four groups were detected by radioligand-receptor binding assay in vitro，behavioral test and small-animal PET. @*Results @# Immunohistochemical staining results of TH at 1-lesion，4-lesion and MFB model showed that the TH-positive cell loss rates of the lesion side in three models were 19. 1% ，84. 7% and 97. 1% ，respectively，indicating that the model was successfully constructed. The results of DAT / D2 receptor functions in the three models showed that，compared with the sham operated control group，the DAT binding ratio of radioactivity on the lesion side of 1-lesion，4-lesion and MFB model significantly decreased (P＜0. 05，P＜0. 05 and P＜0. 01) ．The DAT binding ratio of radioactivity on the lesion side was compared among 1，4 lesion and MFB model．It was found that the decrease degree of MFB model was significantly higher than that of the previous two models (P＜0. 01) ，and the decrease degree of 4-lesion model was significantly higher than that of 1-lesion model (P＜0. 05) ．Compared with the sham operated control group，the D2 receptor binding ratio of radioactivity on the lesion side of 1-lesion and 4-lesion model significantly decreased (P＜0. 05) ， and there was no significant difference in the degree of decrease between the two models，but the D2 receptor binding ratio of radioactivity on the lesion side of MFB model significantly increased (P＜0. 05) ．There was no difference in the distribution of DAT / D2 receptor on the lesion side and the normal side of the sham operated control group．Methamphetamine caused ipsilateral rotations to the lesion side in all models． There were no significant differences in methamphetamine-induced rotation among 1-lesion，4-lesion and MFB models．Bromocriptine caused ipsilateral rotations to the lesion side in 1-lesion and 4-lesion models but contralateral rotations in MFB model. There were no significant differences in bromocriptine-induced rotation between 1-lesion and 4-lesion models．The results of stepping test showed the motion initiation time of the lesion side was significantly longer than that of the normal side，the stepping length of the lesion side was significantly shorter than that of the normal side，and the adjusting steps of the lesion side was significantly less than that of the normal side (P＜0. 001) ，but there was no significant difference of the lesion side in the initiation time ，stepping length ，and adjusting steps among the three groups of models． @*Conclusion@#The striatal lesion and MFB lesion models showed different pathophysiological processes in terms of DA neurotransmitter functions and behavior．The MFB lesion model can mimic primary Parkinson's disease，while the striatal lesion model is similar to some Parkinson syndromes.

Dopamine D1 receptor in ventrolateral periaqueductal gray modulates propofol anesthesia in rats / 医学研究生学报

ObjectiveVentrolateral periaqueductal gray (vlPAG) locates in ascending reticular activating system, which plays a key role in the sleep-wake circle. However, the role of vlPAG in general anesthesia has not been identified. To investigate the effect of the dopamine receptor in vlPAG neurons on propofol anesthesia, we used real-time in vivo fiber photometry, microinjection and EEG.MethodsTo observe the alteration of neuronal activity in the vlPAG throughout propofol anesthesia, 10 Sprague-Dawley rats were used for calcium fiber photometry recording. 50 vlPAG bilateral microinjection models were established and assigned into five groups randomly, including D1R agonist group, D1R antagonist group, D2R agonist group, D2R antagonist group, and control group (n=10). Under propofol anesthesia, 1 μL of D1R agonist, D1R antagonist, D2R agonist, D2R antagonist, and isotonic saline were microinjected into the vlPAG of animals in the corresponding groups, respectively. The induction time, recovery time and the changes in electroencephalogram (EEG) before and after microinjection were recorded and analyzed.ResultsThe neuronal activity in the vlPAG was significantly inhibited during the induction period and markedly recovered during the recovery period from propofol anesthesia (P<0.05). Subsequently, the microinjection of D1R agonist into the vlPAG notably prolonged the induction time and reduced the emergence time of propofol anesthesia with a decrease of δ-band ratio. While the microinjection of D1R antagonist accelerated the induction time and prolonged the emergence time of propofol anesthesia with an increase of δ-band ratio and a decrease in β-band ratio in cortical EEG (P<0.05). The induction and recovery time of D2R agonist /antagonist group did not differ with those of control group. As well, EEG before and after microinjection in D2R agonist /antagonist group did not different.ConclusionThese results indicate that vlPAG modulates the process of propofol anesthesia via D1R.

Association between DNA methylation in the CpG island of dopamine D2 receptor gene promoter region and persistent postural-perceptual dizziness / 中华神经医学杂志

Objective:To analyze the relation between DNA methylation in the CpG island of dopamine D2 receptor ( DRD2) gene promoter region and persistent postural-perceptual dizziness (PPPD), and explore the molecular mechanism of PPPD. Methods:The disease group consisted of 43 patients diagnosed as having PPPD in our hospital from January 2017 to June 2017, and blood samples were taken at admission. The control group included 45 with acute vestibular peripheral vertigo whose dizziness symptoms did not recrudesce after follow-up for more than 3 months and PPPD diagnosis was excluded in our hospital at the same period; these patients did not take selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs); blood samples in the patients were collected during follow-up. DNA methylation in the CpG island of DRD2 promoter region was detected by disulfite sequencing and the differences between the two groups were compared. Results:The positive rate of DNA methylation in the CpG island of DRD2 promoter region in the disease group was 58.1%, which was significantly higher than that in the control group (15.6%, P<0.05); and the methylation rate of CpG island loci in the disease group (0.15±0.18) was significantly higher than that in the control group (0.04±0.10, P<0.05). Conclusion:The DNA methylation in the CpG island of DRD2 promoter region is associated with onset of PPPD.

Effect of Electroacupuncture at "Neiguan" (PC 6) and "Tianshu" (ST 25) for Colonic Motility and D 2 Receptor in Irritable Bowel Syndrome Rats / 针刺研究

OBJECTIVE: To observe and compare the effects of electroacupuncture (EA) at "Tianshu" (ST 25) and "Neiguan" (PC 6) for colonic motility and the expression of colon dopamine D 2 in irritable bowel syndrome (IBS) rats, and to explore the specificity of different meridians and different acupoints. METHODS: Forty Wistar newborn rats were randomly divided into blank, model, Tianshu and Neiguan groups. Separation of mother and child and acetic acid coloclyster combined with colorectal distension were used to establish IBS model in the model, Tianshu and Neiguan groups. At the age of 9 weeks, EA at bilateral ST 25 and PC 6 were applied in the corresponding groups 5 times, once every other day. After the intervention, the Bristol fecal score, the latent period of abdominal retraction reflex and the number of contraction waves were recorded. The expression of dopamine D 2 receptor was detected by immunohistochemistry. RESULTS: Compared with the blank group, the Bristol fecal score of the model group was higher (P<0.01), the 1st contraction wave latent period was shorter (P<0.01), the number of contraction waves in 90 s increased (P<0.01), the immunoreactive expression of D 2 receptor in colon decreased (P<0.01). Compared with the model group, the Bristol fecal scores of the Tianshu and Neiguan groups decreased (P<0.01), the 1st contraction wave latent periods were longer (P<0.01), the numbers of contraction waves in 90 s decreased (P<0.01), the positive expressions of D 2 receptor in colon increased (P<0.01, P<0.05). Compared with the Tianshu group, the immunoreactive expression of D 2 receptor in the Neiguan group decreased (P<0.01). CONCLUSION: EA at ST 25 and PC 6 can improve the symptoms of colonic motility in IBS rats. The effect of EA at ST 25 is better, which indicates that different meridians and different acupoints play specific effects.

Polimorfismos del receptor D2 / D2 receptor polymorphisms

Los prolactinomas son tumores bien diferenciados que se originan en las células lactotropas pituitarias, una línea celular que secreta fisiológicamente prolactina (PRL). A nivel hipofisario, la dopamina está implicada en la regulación de la secreción de PRL por las células lactotropas y este efecto inhibitorio está mediado por la activación del receptor de prolactina tipo 2 (DRD2). Hay varios polimorfismos del DRD2, el primero y más estudiado es TaqI A1; está demostrado que este alelo se encuentra asociado a una reducción de la actividad cerebral dopaminérgica, además de observarse una reducción en su capacidad de unión de aproximadamente un 30%. Este alelo se ha vinculado con una menor densidad de DRD2 en el cuerpo estriado, especialmente en el putamen y caudado ventral, y la cantidad de DRD2 en portadores del alelo A1 fue un 30-40% más bajo que en los no portadores (es decir, TaqI A2 homocigotos). En la literatura, hay evidencia que apoya la posible participación de los polimorfismos DRD2 en la regulación de la secreción hormonal.

Prolactinomas are well differentiated tumours that originate in the pituitary lactotrope cells, a cell line that physiologically secretes prolactin (PRL). At pituitary level, dopamine is involved in the regulation of PRL secretion by lactotropes, and this inhibitory effect is mediated by activation of prolactin type 2 receptor (DRD2). Of the several DRD2 polymorphisms, the first and most studied is TaqI A1. It has been demonstrated that this allele is associated with a reduced dopaminergic brain activity, and a reduction in its binding capacity of approximately 30% also being observed. This allele was associated with a lower density of DRD2 in the striatum, especially in the putamen and ventral caudate. The amount of DRD2 in A1 allele carriers was 30 - 40% lower than in non-carriers (this is, TaqI A2 Homozygotes). There is evidence in the literature, that supports the possible involvement of DRD2 polymorphisms in the regulation of hormonal secretion.

Roles of Dopamine D₂ Receptor Subregions in Interactions with β-Arrestin2

β-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of β-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with β-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with β-arrestin2. For this, we employed dopamine D₂ and D₃ receptors (D₂R and D₃R, respectively), since they display distinct agonist-induced interactions with β-arrestins. Our results showed that the second and third intracellular loops of D₂R are involved in the agonist-induced translocation of β-arrestins toward plasma membranes. In contrast, the N- and C-termini of D₂R exerted negative effects on the basal interaction with β-arrestins.

Functional Regulation of Dopamine D₃ Receptor through Interaction with PICK1

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine D₃ receptors (D₃R), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine D₂ receptor (D₂R) and D₃R in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of D₂R were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of D₃R were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on D₃R functions.

Effects of protocatechuic acid on expression of D2DR, iNOS, and TH in striatum and midbrain of Parkinson's disease model mice / 中草药

The aim of this paper is to investigate the effects of protocatechuic acid (PCA) on the expression of D2DR, iNOS, and TH in striatum and midbrain of Parkinson's disease (PD) mice induced by MPTP. C57BL brown mice were used as experimental animals and were injected with MPTP (25 mg/kg. d) for 7 d to build PD model mice. PCA (10 mg/kg. d) and Madopar (125 mg/kg. d) had been ip administered to the PD mice for the precaution and treatment at the first and lasted for 7 d. The expression of D2DR, iNOS, and TH in the striatum and midbrain of PD mice induced by MPTP was detected by Western blotting method. The results showed that iNOS expression increased while D2DR and TH expression decreased in the striatum and midbrain of MPTP-induced PD mice. However, PCA significantly decreased the expression of iNOS while obviously increased the expression of D2DR and TH in the striatum and midbrain of MPTP-induced PD mice. PCA has a neuroprotective effect on the PD mice induced by MPTP, and its protective effects on mice brain are achieved at least partly by increasing TH and D2DR expression while decreasing iNOS expression.

Effects of Jianpizhidong decoction on dopamine D2 receptor mRNA in striatum of tourette' s syndrome model mice / 中华行为医学与脑科学杂志

Objective To study the effects of traditional Chinese medicine of Jianpizhidong decoction on dopamine D2 receptor(DAD2R) mRNA in tourette syndrome (TS) model mice brain striatum,and provide the proof of neural biochemical for Jianpizhidong decoction in curing children TS.Methods 32 male ICR mice were divided randomly into control group,model group,Jianpizhidong decoction group and Tiapride group.Except control group,all mice in model group,Jianpizhidong decoction group and Tiapride group were made to TS models by intraperitoneal injection of 3,3'-iminodipropionitrile.The control gronp and model group were given normal saline,Jianpizhidong decoction group and Tiapride group were given corresponding drugs by intragastric administration respectively.Results The striatum DATmRNA expression of model group,Tiapride group,and traditional Chinese medicine group decreased(respectively(0.139 ± 0.013),(0.15 ± 0.021),(0.141 ± 0.019)) than that of control group (0.180 ± 0.028),and with 14.1％,3.0％ and 3.9％ down respectively.In model group DATmRNA expression was lower than control group (P ＜ 0.01).In model group DATmRNA expression was lower than Tiapride group (P＜ 0.01).In model group DATmRNA expression was lower than traditional Chinese medicine group (P＜0.01).In Tiapride group DATmRNA expression was lower than traditional Chinese medicine group (P ＜ 0.01).Conclusion The function of improving symptoms of TS by Jianpizhidongtang may be relate to inhibite DAD2R hypersensitization to enhance the activity of substantia nigra-striatum.

A Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for the Detection of DRD2 Polymorphisms

Background: The dopamine D2 receptor gene (DRD2) plays a role in many diseases such as schizophrenia, Parkinson’s disease, and addictive behaviour. Methods currently available for the detection of DRD2 polymorphisms are costly and cannot detect all 8 polymorphisms of our research interest simultaneously (Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, A-241G, and −141C Ins/Del). Therefore, we developed a nested multiplex polymerase chain reaction (PCR) for simultaneous detection of these polymorphisms. Methods: Genomic DNA was extracted from blood using standardised methods. Primers specific at the 3’-end for the polymorphic sites were designed. A two-step PCR method was developed. In the first PCR, a region from exon 3 to 4, exon 7, the promoter region, and the 3’-region of DRD2 were specifically amplified. The products were subsequently used as templates in the second PCR. Sequencing was performed to validate the test results. Results: Specific bands corresponding to the amplified product of interest were obtained. The method was reproducible and specific when used to genotype patients with schizophrenia. The amplified sequences showed 100% homology to the DRD2 sequence. Conclusion: The method was found to be simple, rapid, specific, and reproducible for the simultaneous detection of the DRD2 polymorphisms.

Central Nervous System Drug Evaluation Using Positron Emission Tomography

In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.

Dopamine D2 receptor and transptor mechanism in the prefrontal cortex of the susceptibility to heroin addiction / 中华行为医学与脑科学杂志

Objective To establish the rats model of different susceptibility of heroin addiction,and to explore the possible dopamine D2 receptor (D2R) and dopamine transptor (DAT) mechanism leading to the different susceptibility. Methods 130 male SD rats were carried out CPP training,and the rats were randomly assigned into heroin exposure group (n = 100) and saline control group (SC, n = 30). Heroin exposure group were re-classified into two groups according to the numerical value of the CPP-Pre (the testing score minus that of the pretest):high preference group(HP group) and low preference group(LP group) ,each accounting for 30% of the total rats.The D2R and DAT protein expression of high and low preference group and saline control group rats were detectedwith immunohistochemical method in PFC at 30 minutes and on the 1st,3rd,7th, 14th days after the last injection(149.33 ±2.51 vs 135.83 ±1.78 vs99.33 ±2.84,141.83 ±2.50 vs 131.67 ± 1.87 vs99.17 ±3.61,132.83 ±2.40 vs 122.00 ±2.67 vs 100.33 ±4.26,125.67 ±2.22 vs 113.17 ±2.81 vs 98.33 ±3.25,116.86 ± 1.94 vs 108.63 ± 2.31 vs 98.17 ± 3.82 , respectively, P＜0.05). The D2R protein expressions of HP rats were significantly lower than those of the LP and control group rats (P ＜ 0. 05), and those of LP rat were than lower than those ferent among three groups on addiction phase and 1st,3rd days after the last injection of heroin respectively, respectively (P ＜ 0. 05). The DAT protein expressions of HP and LP rats were significantly lower than those of controlgroup rats (P＜ 0. 05). At all testing time-points, the DAT protein expressions had no significant difference betweenHP and LP group(P＞0. 05). Conclusion D2R and DAT of the rats show appears down-regulation in the PFC after chronic heroin exposure. Different individuals have different D2R sensitivity or receptor levels ,and lower D2R related to the high susceptibility to heroin. Susceptibility to heroin addiction may not be directly related to the expression of DAT.

Role of Dopamine Receptors on Electroencephalographic Changes Produced by Repetitive Apomorphine Treatments in Rats

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5~8 Hz) and alpha (8~13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.

Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6)M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9)M). Dopamine (10(-8)M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6)M). Dopamine (10(-8)M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.

Increased expression of dopamine receptors and transporter and hypomethylation of dopamine transporter gene in uterine leiomyoma / 대한산부인과학회지

OBJECTIVE: Dopamine plays a key role in the proliferation regulation of the smooth muscle cells. The purpose of this study was to observe the degree of expression of dopamine D1 and D2 receptors and dopamine transporter (DAT) and to evaluate the influence of methylation about control of expression of DAT in uterine leiomyoma and normal myometrial tissue. METHODS: In 20 patients who underwent hysterectomy due to uterine leiomyoma, normal myometrial and leiomyoma specimens were obtained. The expression of dopamine D1 and D2 receptors and DAT was demonstrated by using RT-PCR and immunohistochemistry in each normal myometrium and leiomyoma. Analysis of the DNA methylation status of DAT was conducted using HpaII digestion and the methylation-sensitive PCR. RESULTS: The mRNA level of dopamine D1 receptor was relatively higher in normal myometrium than D2 receptor and it was also unchanged in leiomyomas. However, the mRNA levels of dopamine D2 receptor and DAT in leiomyomas were much higher than normal myometrium. Consistent with elevated mRNA levels, high levels of dopamine receptors protein expression were detected by immunohistochemistry in leiomyomas. The degree of methylation at CpG sites of the area intron 1 of DAT (genomic position, +377 - +888) was decreased in leiomyomas. CONCLUSION: These results suggest that overexpressed dopamine D2 receptor and DAT would be associated with proliferation of human uterine leiomyomas and the methylation status of the CpG island of DAT determines its expression.

Effects of Newer Antipsychotic Drugs on Apomorphine-Induced Climbing Behavior in Mice / 대한정신약물학회지

OBJECTIVE: Chlorpromazine equivalence was used to chart relative potencies of typical antipsychotic agents and it has been known to be in a linear relationship with dopamine D2 receptor affinity. After the introduction of these newer antipsychotic drugs, the role of other neurotransmitter systems than dopamine has been emphasized, and it is difficult to attribute the diverse effect of these drugs to common mechanism. Recently, several equivalent dose guidelines have been published for newer antipsychotic drugs. In this study, antagonism of apomorphine-induced climbing behavior was used to investigate the relationship between the clinically determined equivalent doses and behavioral effects measured by animal model of several newer antipsychotic drugs. METHOD: Several newer anti-psychotic drugs were administered 20 min before apomorphine injection. After apomorphine injection, climbing behavior was assessed for up to 20 min by visual inspection. The doses that had inhibited 50% of the control group behavior was defined to be Half-Effective Doses (HED) and calculated from the regression line. The relationship between the HED and clinical Minimum Effective Doses (MED) published elsewhere was investigated using linear regression analysis. RESULT: All the antipsychotic drugs antagonized the apomorphine-induced climbing behavior in a dose-dependent manner. Statistically significant correlation between HED and MED was found (Spearman's rho=0.96, p<0.001), and statistically significant linear relationship was also found (F=76.2, df=1, 4, p=0.001; r2=0.950). CONCLUSION: Antipsychotics inhibit apomorphine-induced climbing behavior by D2 antagonism. Therefore, the result suggests that the common mechanism underlying the therapeutic effects of newer antipsychotics might be related with dopamine D2 antagonism. However, the equivalent doses used in this study focused mainly on psychotic and behavioral symptoms, so that they are not qualified to embrace multi-dimensional therapeutic effects of newer antipsychotics. Investigation of the relationship between the equivalent doses focused on each symptom domain and the effects on diverse neurotransmitter system would broaden our knowledge of mechanism of action of newer antipsychotics.

The Relationship between Taq I A Dopamine D2 Receptor Polymorphism and Therapeutic Response to Antipsychotics in Schizophrenic Patients

PURPOSE: In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine D2 receptor polymorphism in schizophrenic patients. METHODS: The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine D2 receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). RESULTS: The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (chi2(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. CONCLUSIONS: The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

Dopamine D2 Receptor Gene Polymorphism in Cigarette Smoking / 신경정신의학

OBJECTIVE: This study was to examine the effects of DRD2 TaqI A polymorphism on the smoking in Koreans. Also this study examined molecular heterosis and gender difference in the genetic effect of cigarette smoking. METHODS: DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 187 healthy individuals including 94 smokers and 93 non-smokers, RESULTS: Among the total subjects, the smokers were not significantly different from the non-smokers in respect to the frequency and prevalence of A1 allele, the genotype distribution, or the frequency of heterozygotes. Separating the subjects by gender, however, in male subjects smokers showed a significantly higher frequency (p=0.049) and prevalence of A1 allele (p=0.016) than non-smokers. Also, genotype distribution (p=0.055) and frequency of heterozygotes (p=0.058) of smokers showed some different distributions, but there were no significant statistical difference. In contrast, female subjects showed significant difference between smokers and non-smokers in the comparison of frequency of heterozygotes (p=0.018), but not in the comparison of the frequency (p=0.582) and prevalence (p=0.082) of A1 allele and genotype distribution (p=0.060). CONCLUSION: No significant difference between smokers and non-smokers in the genotype distributions of the total sample could be explained by the reciprocal effects of gender difference in the genetic effect of DRD2 A1 allele of the smoking. Our findings support gender difference and molecular heterosis at the DRD2 gene effects of smoking.

Association between a DRD_2 Marker (TaqIA) and Heroin Dependence / 中国心理卫生杂志

Objective:to explore the relation of a marker (TaqIA) located DRD 2 gene and heroin dependence.Method:to compare the genotypes and allele frequencies between 66 patients with heroin dependence and 132 normal controls by PCR-RELP. TABPQ was used to measure the characters of patient's behavior.Result:There were significant differences in allele frequencies between patients and controls. No behavior difference was found between patients with different genotypes. Conclusion:There is an association between the marker (TaqIA) and heroin dependence. The data suggest that patients with A1 allele confers susceptibility to heroin dependence.

Relationship between DRD2 - 141C Ins/Del Polymorphism and Heroin Craving / 中国临床心理学杂志

Objective:To explore the relationship between DRD2 - 141C Ins/Del polymorphism and heroin craving. Methods:380 heroin addicts who were under abstinence were given the cue- elicited heroin craving experiment. And then we detected the polymorphism of DRD2- 141CIns/Del for them by using PCR- RFLP. We compared the relationship between genotypes of DRD2- 141CIns/Del and heroin craving before and after cue exposure. Results:No significant differ- ence has been found between heroin craving before and after cue- exposure in three genotypes of DRD2- 141CIns/Del. Conclusion:D2 receptor gene - 141CIns/Del polymorphisms may have no association with the susceptibility of heroin crav- ing.