Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.
Antipsychotic Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; China ; Genome-Wide Association Study ; Genotype ; Humans ; Lipid Metabolism ; genetics ; Neurosecretory Systems ; drug effects ; Pharmacogenomic Testing ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; genetics ; Receptors, Dopamine ; genetics ; Receptors, Histamine ; genetics ; Receptors, Serotonin ; genetics ; Weight Gain ; drug effects ; genetics

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D₂ receptor bindings with strong binding to the 5-HT(2A) receptor, while typical antipsychotics block long-lasting, tight D₂ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.
Affective Symptoms ; Analgesics ; Antidepressive Agents ; Antipsychotic Agents ; Delusions ; Dopamine ; Drug-Related Side Effects and Adverse Reactions ; Dystonia ; Hallucinations ; Histamine ; Humans ; Movement Disorders ; Norepinephrine ; Pain Management ; Prolactin ; Psychomotor Agitation ; Psychotic Disorders ; Receptor, Serotonin, 5-HT2A ; Receptors, Neurotransmitter ; Serotonin ; Weight Gain

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAreceptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABAand NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.
Animals ; Benzazepines ; pharmacology ; Cells, Cultured ; Cochlea ; cytology ; Neurons ; drug effects ; Rats ; Receptors, Dopamine ; metabolism ; Receptors, GABA-A ; metabolism ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Sodium Salicylate ; toxicity ; Spiral Ganglion ; drug effects

OBJECTIVETo compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction.

METHODSVentricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined.

RESULTSCardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01).

CONCLUSIONSThe administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.

Adenylyl Cyclases ; metabolism ; Animals ; Blotting, Western ; Cardiac Output ; drug effects ; Cardiopulmonary Resuscitation ; Cyclic AMP ; metabolism ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Epinephrine ; blood ; Heart Ventricles ; drug effects ; metabolism ; physiopathology ; Hemodynamics ; drug effects ; Injections ; Male ; Myocardium ; enzymology ; pathology ; Norepinephrine ; blood ; Receptors, Adrenergic, beta-1 ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Swine ; Swine, Miniature ; Up-Regulation ; drug effects

OBJECTIVETo study the effects of low concentration dopamine(DA) on hydrogen peroxide-induced apoptosis in cultured rat cardiomyocytes as well as the possible molecular mechanisms.

METHODSCultured neonatal rat cardiomyocytes were randomly divided into the following groups: control group (control), hydrogen peroxide group (H2O2), pretreated with low concentration dopamine ( DA + H2O2), dopamine receptor l(DR1) antagonist group (DR1 + DA + H2O2), dopamine receptor 2(DR2) antagonist group (DR2 + DA + H2O2). The cell apoptosis was then assessed by MTT and flow cytometry. The cellular ultrastructure changes were observed by transmission electron micro- scope. The activity of lactate dehydrogenase(LDH )and superoxide dismutase (SOD) in cell medium was analyzed by colorimetry. The protein expressions of Cytochrone c, Caspase 3 and Caspase 9 were obtained by Western blot.

RESULTSCompared with hydrogen peroxide group, low concentration dopamine(10 µmol/L) decreased the apoptosis rate and the expression of protein of apoptosis related protein, enhanced SOD activity, decreased LDH activity. DR1 antagonist SCH-23390 treatment inhibited dopamine induced cardiac protective effect. DR2 antagonist haloperido treatment had no changes compared with dopamine group.

CONCLUSIONAbove findings indicate that low concentration dopanine inhibits apoptosis induced by hydrogen peroxide in neonatal rat cardiomyocytes, which is partly associated with the activation of DR1.

Animals ; Apoptosis ; Benzazepines ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Dopamine ; pharmacology ; Hydrogen Peroxide ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats ; Rats, Wistar ; Receptors, Dopamine D1 ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects.

METHODThe CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors.

RESULTCompared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05).

CONCLUSIONThe down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Animals ; Berberine Alkaloids ; administration & dosage ; Brain ; drug effects ; metabolism ; physiopathology ; Conditioning, Operant ; drug effects ; Corydalis ; chemistry ; Dopamine ; metabolism ; Humans ; Male ; Morphine ; adverse effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; genetics ; metabolism ; Substance-Related Disorders ; drug therapy ; genetics ; metabolism ; psychology

OBJECTIVETo explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD).

METHODSA total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats.

RESULTSBHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05).

CONCLUSIONBHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.

Animals ; Brain ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Parkinson Disease ; drug therapy ; metabolism ; Phytotherapy ; Rats ; Receptors, Dopamine D2 ; drug effects ; metabolism

OBJECTIVETo detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells and investigate the effect of dopamine in inducing apoptosis of A549 cells.

METHODSWestern blotting and RT-PCR were employed to detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells (95D, H460, GLC-82, A549 and H446 cells). The apoptosis of A549 cells after a 6-hour exposure to 0.02%, 0.04%, 0.08% and 0.1% dopamine was analyzed by flow cytometry. The apoptosis-inducing effect of dopamine in vivo was also tested by intratumoral injection of 1% dopamine in 2 BALB/c-nu mice bearing A549 tumor xenograft using flow cytometry.

RESULTSThe presence of dopamine receptor D2 expression was detected by Western blotting and RT-PCR in 95D, H460, GLC-82, A549 and H446 cells. Flow cytometry detected obvious apoptosis of A549 cells following dopamine exposure in vitro in positive correlation to dopamine concentration. In the tumor-bearing mice, dopamine also showed an obvious apoptosis-inducing effect on A549 cells.

CONCLUSIONDopamine receptor D2 exists extensively in different pulmonary carcinoma cells. Dopamine may promote the apoptosis of pulmonary carcinoma cells through dopamine receptor D2.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Dopamine ; pharmacology ; Flow Cytometry ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptors, Dopamine D2 ; metabolism

OBJECTIVETo investigate the role of dopamine-1 receptor in the modulation of basic respiration rhythm.

METHODSNewborn SD rat (0-3 days, n=20) brain stem slices containing the medial region of the nucleus retrofacialis (mNRF) were prepared with the hypoglossal nerve roots retained. The respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve was recorded using suction electrodes on these preparations, and the effects of dopamine-1 receptor on RRDA were investigated by application of the specific agonist of dopamine-1 receptor A68930 at different concentrations (0, 1, 2, and 5 micromol/L) in the perfusion solution.

RESULTSThe respiratory cycles (RC) and the expiratory time (TE) decreased progressively with gradual increment of the integrated amplitude (IA) after A68930 administration, and their changes were the most conspicuous at 5 min after the administration. A68930 at the concentrations of 2 and 5 micromol/L resulted in the most obvious changes in RC, TE, and IA (P<0.05), but IA exhibited no significant variation at 1 min after perfusion with 2 micromol/L A68930 (P>0.05). RC and TE were gradually shortened after treatment with increasing concentrations of A68930, which also caused gradual increment of IA, and at the concentration of 5 micromol/L, RC, TE, and IA all showed the most obvious changes (P<0.01).

CONCLUSIONSDopamine-1 receptor plays a role in the modulation of RRDA in isolated neonatal rat brainstem slice. A68930 may increase the frequency of respiration by shortening TE and enhance the respiratory activity by increasing the amplitude of inspiratory discharge of the respiratory neurons.

Animals ; Animals, Newborn ; Cell Separation ; Chromans ; pharmacology ; Dopamine Agonists ; pharmacology ; In Vitro Techniques ; Medulla Oblongata ; cytology ; physiology ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine ; physiology ; Respiration ; drug effects

OBJECTIVETo evaluate the effect of Qufeng Zhidong Recipe (QZR) on the head tic behavior, and the mRNA expressions of Notch1 and dopamine D2 receptor (D2R) in tic disordered mice.

METHODSMouse model like wet-dog shake head tic disorder was established by peritoneal injection of 5-HT2A/C agonist DOI for 14 successive days. The model mice were divided into three groups, the model group, the Chinese medicine (CM) treated group and the Western medicine (WM) treated group, they were intervened respectively with distilled water, QZR (10 g/kg) and haloperidol (1 mg/kg). Besides, a normal control group was set up and gastrogavaged with distilled water. The effect of intervention was evaluated 2 weeks later by estimating the head tic and the creeping distance of animals, and the mRNA expressions of D2R and Notch1 in corpus striatum and prefrontal cortex regions were detected using Real-time PCR.

RESULTSThe wet-dog shake response and the creeping distance of mice were significantly reduced after intervention in both intervened groups, showing insignificant difference between the effects of CM and WM (P > 0.05). The expression of D2R mRNA in corpus striatum was higher than that in the prefrontal cortex (P < 0.01), at the prefrontal cortex, it was 151 +/- 30 in the CM group and 180 +/- 41 in the WM group, and at the corpus striatum, 710 +/- 64 and 850 +/- 80 respectively, all higher than those in the model group (P < 0.05). While the Notch1 mRNA expression in model mice were lower at the prefrontal cortex than at the corpus striatum (P < 0.05). After intervention it was 55 +/- 20 in the CM group and 48 +/- 23 in the WM group at the prefrontal cortex, all significantly lower than that in the model group (P < 0.05).

CONCLUSIONDOI-induced wet-dog shake response could well simulate the clinical characteristics of tic disorder; QZR could improve the tic behavior and creeping distance in the model mice. The up-regulation of D2R mRNA expression after QZR intervention may be related with the down-regulation of Notch1 expression, this findings is worthy of further studies.

Animals ; Corpus Striatum ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Receptor, Notch1 ; genetics ; metabolism ; Receptors, Dopamine D2 ; genetics ; metabolism ; Signal Transduction ; drug effects ; Tic Disorders ; drug therapy