Two new sesquiterpenoid glycoside compounds from the calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-ß-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3-12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 µM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 µM, respectively.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

Analysis of related parameters of ocular biometric values in children and adolescents / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To measure ocular biometric values with sexual and age and determine the relationship between the differences using the Lenstar 900.METHODS:Totally 413 myopes 826 eyes,200 males (400 eyes) and 213 females (426 eyes),were enrolled in this study and were divided into 3 groups:Group Ⅰ (＜ 5 years),Group Ⅱ (5-10 years),Group Ⅲ (＞10 years).Central corneal thickness (CCT),anterior chamber depth (ACD),lens thickness (LT),axial length (AL),white-to-white distance (WWD) and pupil diameter (PD) were measured by Lenstar 900.The differences between age groups and gender groups were compared using the LSD and SNKk methods in variance analysis.Pearson correlation coefficient to assess AL,CCT,ACD,LT,WWD,PD in children and adolescents.RESULTS:There were significant difference in CCT between ages groups (P＜0.05) which increased with the age.There were significant differences both in ACD and AL between sexual groups.With analysis of Person,CCT showed a significantly positive correlation with WWD and PD(r=0.208,0.167;P＜0.05) and ACD showed a significantly positive correlation with AL,WWD,PD(r=0.620,0.238,0.192;P＜0.05).LT showed a significantly negative correlation with ACD,AL and WWD (r=-0.271,-0.186,-0.227;P＜0.05).WWD showed a significantly positive correlation with PD (r=0.273,P＜0.05).CONCLUSION:CCT has gradually thickening trend with ages.Men are more than women in ACD and AL.CCT shows positive correlation with WWD and PD and ACD shows positive correlation with AL,WND,PD.LT shows negative correlation with ACD,AL and WWD.WWD showed positive correlation with PD.

Facial emotion recognition and alexithymia in Chinese male patients with deficit schizophrenia.

Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct schizophrenia subtype. This study investigated facial emotion recognition deficits and alexithymia in DS and non-deficit schizophrenia patients (NDS) and their relationships with other clinical variables. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Scale for the Assessment of Positive Symptoms (SAPS) were employed to evaluate the psychiatric symptoms in patients with schizophrenia. Facial emotion recognition deficits and Alexithymia were assessed in DS, NDS, and control groups by The Chinese Facial Emotion Test (CFET) and the Toronto Alexithymia Scale-20 (TAS-20). Compared with control group, both DS and NDS patients exhibited more severe facial emotion recognition impairments, with the exception of "happy faces" in NDS patients, as well as higher alexithymia scores. In DS patients, correct frequency for fear recognition and total CFET score were negatively correlated with TAS-20 Factor 3 subscore for "externally oriented thinking". Total TAS-20 score was positively correlated with BPRS negative symptom and SANS score in DS patients. In contrast, there were no correlations between TAS-20 scores/subscores and psychiatric symptoms in NDS patients. These findings indicated distinct facial emotion recognition impairments in DS and NDS patients. Alexithymia might be specifically related to the negative symptom in DS patients, suggesting DS as a unique schizophrenic subtype.

Synthesis, physicochemical characterization and pharmacological investigation of indolacin-5-fluorouracil-1-ylmethyl ester.

The objective of this work is to synthesize indolacin-5-fluorouracil-1-ylmethyl ester and the structure was confirmed by means of UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The physicochemical parameters of melting point, solubility, apparent partition coefficient were investigated. S180 sarcoma, H22 hapatitic cancer and Lewis-transplanted mice were used to evaluate the anti-tumor activity of indolacini-5-fluorouracil-1-ylmethyl ester compared with 5-fluorouracil in vivo. Anti-inflammatory and analgesic activities were evaluated in mice. The inhibitory ratio of indolacini- 5-fluorouracil-1-ylmethyl ester is comparative to that of 5-fluorouracil. This study indicates that 5-fluorouracil-1-ylmethyl ester may represent a new anticancer predrug of 5-fluorouracil to produce a combined effect of indolacin and 5-fluorouracil for cancer therapy.

The Role of the Two-Pore Domain Potassium Channel TREK-1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression.

AIM: Poststroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. TREK-1, a two-pore-domain potassium channel, has been implicated in the pathogenesis of stroke and depression. The aim of this study was to investigate whether TREK-1 plays a role in the therapeutic effects of the selective serotonin reuptake inhibitor (SSRI) escitalopram in a rat PSD model. METHODS: The whole-cell patch-clamp technique was performed to assess the effect of escitalopram on recombinant TREK-1 currents in HEK293 cells. The expression of TREK-1 mRNA and protein was measured in the hippocampus and prefrontal cortex (PFC), and neural stem cell (NSC) proliferation was detected in the hippocampal dentate gyrus (DG) in PSD rats after 3 weeks of escitalopram administration. RESULTS: Escitalopram reversibly inhibited TREK-1 currents in a concentration-dependent manner. Chronic treatment with escitalopram significantly reversed the reductions in weight gain, locomotor activity, and sucrose preference in PSD rats. The expressions of TREK-1 mRNA and protein were significantly increased in hippocampal CA1, CA3, DG, and PFC in PSD rats, with the exception of TREK-1 mRNA in hippocampal CA1. NSC proliferation was significantly decreased in hippocampal DG of PSD rats. Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats. CONCLUSION: TREK-1 plays an important role in the therapeutic effects of the SSRI escitalopram in PSD model, making TREK-1 an attractive candidate molecule for further understanding the pathophysiology and treatment of PSD.

Selective vulnerability related to aging in large-scale resting brain networks.

Normal aging is associated with cognitive decline. Evidence indicates that large-scale brain networks are affected by aging; however, it has not been established whether aging has equivalent effects on specific large-scale networks. In the present study, 40 healthy subjects including 22 older (aged 60-80 years) and 18 younger (aged 22-33 years) adults underwent resting-state functional MRI scanning. Four canonical resting-state networks, including the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN) and salience network, were extracted, and the functional connectivities in these canonical networks were compared between the younger and older groups. We found distinct, disruptive alterations present in the large-scale aging-related resting brain networks: the ECN was affected the most, followed by the DAN. However, the DMN and salience networks showed limited functional connectivity disruption. The visual network served as a control and was similarly preserved in both groups. Our findings suggest that the aged brain is characterized by selective vulnerability in large-scale brain networks. These results could help improve our understanding of the mechanism of degeneration in the aging brain. Additional work is warranted to determine whether selective alterations in the intrinsic networks are related to impairments in behavioral performance.

UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma: application to pharmacokinetic study after administration emulsion of the isomer.

ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. MATERIALS AND METHODS: Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. RESULTS: The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration.

Levels of 1,25(OH)2D3 for patients with pulmonary tuberculosis and correlations of 1,25(OH)2D3 with the clinical features of TB.

BACKGROUND: To determine the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentrations to patients with tuberculosis (TB) and whether it influenced the patient's clinical features. METHODS: For the first part, a total of 153 healthy adults and 74 patients with pulmonary TB (PTB) were enrolled. Serum concentrations of 1,25(OH)2D3 were determined by liquid chromatography-tandem mass spectroscopy to examine the 1,25(OH)2D3 concentrations of the two groups from the peripheral blood. If there are differences between the two groups, what follow will increase the experimental group numbers to examine the relationship among the 1,25(OH)2D3 concentrations with the numbers of the lesion area, the tubercule bacilli in sputum and the CD4/CD8 ratio of T lymphocytes in the peripheral blood. RESULTS: In the first part, the 1,25(OH)2D3 concentrations was lower in patients with TB than in those healthy adults [365.9 (SD 235.7) vs. 464.3 (SD 335.6), P<0.05]. In the second part, we increased the sample size to 134 (male 91 cases, female 43 cases). we found that the plasma levels of 1,25(OH)2D3 are not correlated with the numbers of the lesion area and the tubercule bacilli in sputum, but the 1,25(OH)2D3 levels can interact the ratio of CD4/CD8 T lymphocytes, it shows a positive correlation with the ratio of CD4/CD8 T lymphocytes. CONCLUSIONS: The 1,25(OH)2D3 concentrations in TB patients lower than the healthy adults, it might exist as a risk factor during the development of TB or TB might affect the levels of 1,25(OH)2D3. But the different status vitamin D concentration might not affect the numbers of the lesion area, the tubercule bacilli in sputum. It shows a positive correlation with the ratio of CD4/CD8 T lymphocytes. The study will have a significance value to clinical medicine, but further study will need to study the levels of 1,25(OH)2D3 with the TB.

Protein kinase Mζ is involved in the modulatory effect of fluoxetine on hippocampal neurogenesis in vitro.

The efficacy of chronic selective serotonin reuptake inhibitors (SSRIs) on depression is paralleled by the recovery of deficits in hippocampal neurogenesis related to sustained stress and elevated glucocorticoids. Previous studies have shown that atypical protein kinase C (aPKC) is implicated in the regulation of neurogenesis and the antidepressant response. Whether the specific aPKC isoforms (PKCζ, PKMζ and PKCι) are involved in SSRI-induced hippocampal neurogenesis and the underlying mechanisms is unknown. The present study shows that PKMζ and PKCι but not PKCζ are expressed in rat embryonic hippocampal neural stem cells (NSCs), whereas PKMζ but not PKCι expression is increased by the SSRI fluoxetine both in the absence and presence of the glucocorticoid receptor agonist dexamethasone. PKMζ shRNA significantly decreased neuronal proliferation and neuron-oriented differentiation, increased NSC apoptosis, and blocked the stimulatory effect of fluoxetine on NSC neurogenesis. Fluoxetine significantly increased PKMζ expression in hippocampal NSCs in a 5-hydroxytryptamine-1A (5-HT1A) receptor-dependent manner in both the absence and presence of dexamethasone. The PKMζ peptide blocker ZIP and MEK inhibitor U0126 significantly inhibited the increase in extracellular signal-regulated kinase 1/2 and cyclic adenosine monophosphate response element binding protein phosphorylation in the mitogen-activated protein kinase (MAPK) pathway and hippocampal NSC neurogenesis in response to fluoxetine and the 5-HT1A receptor agonist 8-OH DPAT. Collectively, our results suggest that the SSRI fluoxetine increases hippocampal NSC neurogenesis via a PKMζ-mediated mechanism that links 5-HT1A receptor activation with the phosphorylation of the downstream MAPK signaling pathway.

Classification tree analysis of the factors influencing injury-related disability caused by the Wenchuan earthquake.

OBJECTIVE: To identify the factors that influenced the risk of injury-related disability caused by the Wenchuan earthquake. METHODS: A chi-squared automatic interaction detection (CHAID) classification tree analysis was used to retrospectively analyse clinical data from patients who underwent surgical treatment for earthquake-related injuries in the first 5 days after the earthquake. The CHAID classification tree explored the relationships between the development of disability and potential influencing factors including sex, age, time interval between injury and treatment, wound type, preoperative and postoperative haemoglobin levels, and operation time. RESULTS: A total of 334 patients underwent surgery; of these, 113 (33.8%) were discharged with varying degrees of permanent disability. The CHAID classification tree showed that children (≤ 17 years old), a long time interval between injury and treatment, an open wound and a low preoperative haemoglobin level were significant risk factors for disability. CONCLUSION: The results of this study can help to stratify patients according to their medical needs and to help allocate the available resources efficiently to ensure the best outcomes for injured patients during future earthquakes.

Methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphism is associated with antipsychotic-induced weight gain in first-episode schizophrenia.

Genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism may be important predictors of antipsychotic drug-induced weight gain (AIWG). We tested whether two functional MTHFR polymorphisms are related to AIWG. Weight gain was studied in two cohorts of first-episode, initially drug-naive schizophrenia patients; Chinese Han (n = 182) and Spanish Caucasians (n = 72) receiving antipsychotics for 10 wk and 3 months respectively. Blood DNA was genotyped for 677C/T and 1298A/C MTHFR polymorphisms. Patients with the 677 CC genotype had a significantly greater increase in BMI compared to T-allele carriers in both Chinese (p = 0.012) and Spanish (p = 0.017) samples. The 677C/T MTHFR polymorphism showed an additive effect, but no significant interaction, with the -759C/T HTR2C polymorphism previously associated with AIWG. These results suggest that the 677C/T MTHFR polymorphism might, along with the -759C/T HTR2C polymorphism and other genetic factors, provide a useful marker for the important and limiting side effect of AIWG.

The association between the disruption of motor imagery and the number of depressive episodes of major depression.

BACKGROUND: Mental rotation performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. Previous studies suggest depressive patients present the correlates of impaired behavioural performance for mental rotation and psychomotor disturbance. The aim of this study is to compare the mental rotation abilities of patients with a first episode of depression, recurrent depression and healthy control subjects with regard to hand tasks. METHODS: We tested 32 first episode of depression, 38 recurrent depression and 36 healthy control subjects by evaluating the performance of depressed patients with regard to the hand mental rotation tasks. RESULTS: First, the first episode and recurrent depression subjects were significantly slower and made more errors than controls in mentally rotating hands. Second, the first depressive episode but not the recurrent depression displayed the same pattern of response times to stimuli at various orientations relative to control subjects in the hand task. Third, in particular, recurrent depression subjects were significantly slower and made more errors during the mental transformation of hands than first depressive episode relative to control subjects and the differences were significantly larger in female than male subjects in the mental rotation hand task. LIMITATIONS: Patients were on antidepressant medication. CONCLUSIONS: These results suggest that the impaired behavioural performance for mental representation processing are related to the number of previous episodes. Moreover, the recurrent major depressive episodes may contribute to the reinforcement of cognitive impairments and further the development or maintenance of mental representation dysfunctions, especially in female patients. A deficit on mental rotation in the depressive patients may be potential biomarkers for recurrence chronically.

In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets.

The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.

The effect of chronic antipsychotic drug on hypothalamic expression of neural nitric oxide synthase and dopamine D2 receptor in the male rat.

Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS) and dopamine D2 receptor (DRD2) in the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days' antipsychotic drug administration on expression of nNOS and DRD2 in the rat hypothalamus. Haloperidol (0.5 mg/kg/day i.p.) significantly decreased nNOS integrated optical density in a sub-nucleus of the MPOA, medial preoptic nucleus (MPN), and decreased the nNOS integrated optical density and cell density in another sub-nucleus of the MPOA, anterodorsal preoptic nucleus (ADP). Risperidone (0.25 mg/kg) inhibited the nNOS integrated optical density in the ADP. nNOS mRNA and protein in the MPOA but not the PVN was also significantly decreased by haloperidol. Haloperidol and risperidone increased DRD2 mRNA and protein expression in both the MPOA and the PVN. Quetiapine (20 mg/kg/day i.p.) did not influence the expression of nNOS and DRD2 in either the MPOA or the PVN. These findings indicate that hypothalamic nNOS and DRD2 are affected to different extents by chronic administration of risperidone and haloperidol, but are unaffected by quetiapine. These central effects might play a role in sexual dysfunction induced by certain antipsychotic drugs.

Sexual dysfunction in male schizophrenia: influence of antipsychotic drugs, prolactin and polymorphisms of the dopamine D2 receptor genes.

AIM: Sexual dysfunction induced by antipsychotic drug treatment is under investigated and under reported. This study aimed to determine the influence of genetic polymorphisms in the D2 dopamine receptor (DRD2) and endothelial nitric oxide synthase (eNOS) genes, and the possible role of blood prolactin concentrations on sexual function in schizophrenic patients. MATERIALS & METHODS: Male remitted schizophrenic patients (n = 100), who were living with a sexual partner and receiving antipsychotic drug monotherapy for at least 6 months, were assessed for sexual and erectile dysfunction using the Arizona Sexual Experience Scale and the five-item version of the International Index of Erectile Function. Blood samples were taken for plasma prolactin determination and genotyped for four polymorphisms: DRD2 (-141C Ins/Del and Taq1A) and eNOS gene (G894T and T-786C). RESULTS: The -141C Ins/Del, but not Taq1A, polymorphism of the DRD2 gene was significantly associated with sexual dysfunction with the del allele being less frequent in sexual dysfunction subjects. Neither of the eNOS polymorphisms, G894T or T-786C, was significantly associated with sexual or erectile dysfunction. Prolactin concentrations were significantly higher in patients with erectile dysfunction but did not reach significance in those with sexual dysfunction. Prolactin was also reduced in -141C Del allele carriers. The frequency and severity of sexual dysfunction in the patients receiving typical antipsychotics was significantly greater than those receiving risperidone or clozapine, while prolactin concentrations were significantly higher in subjects receiving risperidone compared with those receiving clozapine or typical antipsychotics. CONCLUSION: This is the first evidence indicating that antipsychotic drug treatment in men is associated with a variant in the DRD2 gene in which the -141C Del allele might be a protective factor. While this may, in part, be mediated by effects on prolactin, other factors are likely to contribute to the greater sexual dysfunction in patients receiving typical antipsychotics.

Expression of ß-catenin and cyclin D1 in epidermal stem cells of diabetic rats.

The healing of diabetic wounds represents a formidable clinical challenge, and the molecular mechanisms involved in diabetic wound healing are far from clear. In this study, we investigated the expression of ß-catenin and cyclin D1 in the epidermal stem cells (ESCs) of diabetic rats, and explored whether the reduction of ß-catenin and its downstream target in ESCs, cyclin D1, lead to poor wound healing in diabetes mellitus (DM). We found that, compared to the controls, the ESCs of diabetic rats were markedly reduced, the clone formation efficiency of the ESCs was markedly lower, and the mRNA and protein expression of ß-catenin and cyclin D1 was significantly decreased. These findings suggest that the low expression of ß-catenin and cyclin D1 may reduce the activity of ESCs from diabetic rats, which might be one of the important mechanisms of delayed wound healing in DM.

Hippocampal neurochemistry is involved in the behavioural effects of neonatal maternal separation and their reversal by post-weaning environmental enrichment: a magnetic resonance study.

Exposure to early life stress results in behavioural changes, and these dysfunctions may persist throughout adulthood. In this study, we investigated whether hippocampus volume and neurochemical changes were involved in the appearance of these effects in the maternal separation (MS) animal model using the noninvasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Sprague-Dawley rats exposed to MS for 180 min from postnatal days (PND) 2-14 demonstrated decreased sucrose preference, increased immobility in the forced swimming test (FST), and impaired memory in the Morris water maze in adulthood. Environmental enrichment (EE) (PND 21-60) could ameliorate the effects of MS on sucrose preference and learning and memory but not on immobility in the FST. In addition, EE significantly increased N-acetylaspartate (NAA) of MS animals. However, we did not find an effect of MS or EE on hippocampal volume. These results indicate the involvement of hippocampal neurochemistry in the behavioural changes that result from early stressful life events and their modification by post-weaning EE. Thus changes in NAA, as a measure of neuronal integrity, appear to be a sensitive correlate of these behavioural effects.

The dose-dependent effect of chronic administration of haloperidol, risperidone, and quetiapine on sexual behavior in the male rat.

INTRODUCTION: Antipsychotic drug-induced sexual dysfunction is a common and problematic side effect, which may diminish quality of life and lead to treatment noncompliance. Up to date, there is still a scarcity of basic research regarding the chronic effects of most antipsychotic agents on sexual behavior. AIM: The present study investigated the effect of a range of doses of three antipsychotic drugs (haloperidol, risperidone, and quetiapine) on male rat sexual competence following chronic administration. METHODS: Twelve groups of Sprague-Dawley rats (n = 7 each) received by gavage haloperidol (0.25, 0.5, or 1 mg/kg), risperidone (0.125, 0.25, or 0.5 mg/kg), quetiapine (10, 20, and 40 mg/kg) or vehicle (distilled water) in the corresponding control groups, respectively, once daily for 21 days. Sexual function was evaluated by the copulatory behavior test 10 hours after the last dose. MAIN OUTCOME MEASURE: The male rat behavioral parameters of copulatory test. RESULTS: Sexual function was widely and significantly suppressed by high dose haloperidol (1 mg/kg) after 21 days administration compared with the control group, which included both frequency and latency of intromission and ejaculation. Only ejaculation latency was significantly impaired after administration with 0.5 mg/kg haloperidol. Compared with the control group, high dose risperidone (0.5 mg/kg) significantly decreased the frequency of mounting. There were no significant changes in sexual behavior with the lower doses of either haloperidol or risperidone. Sexual behavior was not influenced by any dose of quetiapine. CONCLUSIONS: Haloperidol and risperidone, but not quetiapine, could impair sexual competence in a dose-related manner in male rats.