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1.
Evidence has been reported that clozapine may derive part of its therapeutic effects in treatment-resistant schizophrenic patients by interacting with the serotonin system. Among the few behavioural models available to test the hypothesis of an interaction of clozapine with 5-HT2 receptors, male rat sexual behaviour is particularly useful, since in this behaviour 5-HT1A and 5-HT2 receptors have opposite functions. Stimulation of 5-HT1A receptors facilitates ejaculatory behaviour and stimulation of 5-HT2 receptors inhibit ejaculation. In the present study, male rat sexual behaviour was depressed by treatment with DOI (1.0 mg/kg), a selective 5-HT2 receptor agonist. The depressive effect of DOI was attenuated by the administration of clozapine (0.1–1.0 mg/kg) in doses that by themselves did not significantly affect sexual behaviour. It was concluded that clozapine in the male rat sexual behaviour model may be interpreted as serving as a 5-HT2 antagonist. 相似文献
2.
Yasukazu Kuroda Masahiko Mikuni Tetsuo Ogawa Kiyohisa Takahashi 《Psychopharmacology》1992,108(1-2):27-32
The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the Bmax values for3H-ketanserin binding without any change in the Kd values. Moreover, this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI. 相似文献
3.
武陵地区民间146种“七”药考证与分析 总被引:5,自引:0,他引:5
为统一对民族民间“七”药的认识,解决“七”药命名中同物异名或同名异物的难题,经过多年对武陵地区“七”药的实地考察和核对有关标本,文献,考证出了该地区146种“七”药的名实,分析了“七”药的生态环境,基原,性味,功效及化学成分。并对“七”药的科学命名和应用开发提出了建议。 相似文献
4.
Rationale: Defining the mechanism of tolerance development to hallucinogenic drugs will help to explain their mechanism of action. Objectives: The present study was conducted to determine first, if tolerance develops to the discriminative stimulus (DS) properties
of the hallucinogen, 2,5 dimethoxy-4-iodo-amphetamine (DOI) and second, the mechanism mediating tolerance. Methods: Rats were trained to discriminate 0.75 mg/kg DOI from saline on a concurrent VI-30-min schedule of reinforcement with a
15-min time-out for incorrect responses. To evaluate tolerance development, rats were assigned to one of four groups and treated
with either chronic saline or chronic DOI. Prior to chronic treatment, two groups were tested for choice behavior following
vehicle administration while the remaining two groups were tested following the administration of 0.375 mg/kg DOI. One group
from each pre-test condition was injected with either saline or DOI (1 mg/kg) for 8 days. Twenty-four hours after the last
chronic injection the pre-test treatments were replicated. Using receptor autoradiography, the density of 5-HT2A and 5-HT2C receptors was measured in independent groups of rats that had received identical treatment conditions. Results: Animals receiving chronic DOI showed a 60% decrease in DOI lever responding (from 100% to 40%) when tested on 0.375 mg/kg
DOI, while animals receiving chronic saline showed no change in percent choice (100%) on the DOI lever. Significant changes
in binding were observed in 5-HT2A receptors but not 5-HT2C receptors. The results of tests with antagonists were consistent with the changes in binding. Conclusions: These results suggest that behavioral tolerance to DOI reflects neuroadaptive changes in 5-HT2A receptors.
Received: 17 July 1998 / Final version: 19 January 1999 相似文献
5.
Zvi Steve Yadin 《Contemporary psychoanalysis》2016,52(4):547-577
A first name captures indispensable information about its bearer, including aspects of the individual's inner world and approach to the environment, the aspirations and attributions of the name-givers for the individual, and the transferences and countertransferences involving the feelings that a first name evokes. A name is therefore a code waiting to be deciphered that, when explored, can reveal its significance to its bearer. A name can impart multiple meanings; the process of interpreting a name is akin to peeling an onion layered in infinite sequences. This article proposes that an examination of the analysand's first name can be a useful clinical tool in psychoanalytic therapy. An exploration into the origin and meaning of a patient's first name through detailed inquiry and association can serve as a rich source of insight regarding relationships between name and self-identity, and can quickly expand the analytic process. 相似文献
6.
BackgroundPrevious state-of-the-art systems on Drug Name Recognition (DNR) and Clinical Concept Extraction (CCE) have focused on a combination of text “feature engineering” and conventional machine learning algorithms such as conditional random fields and support vector machines. However, developing good features is inherently heavily time-consuming. Conversely, more modern machine learning approaches such as recurrent neural networks (RNNs) have proved capable of automatically learning effective features from either random assignments or automated word “embeddings”.Objectives(i) To create a highly accurate DNR and CCE system that avoids conventional, time-consuming feature engineering. (ii) To create richer, more specialized word embeddings by using health domain datasets such as MIMIC-III. (iii) To evaluate our systems over three contemporary datasets.MethodsTwo deep learning methods, namely the Bidirectional LSTM and the Bidirectional LSTM-CRF, are evaluated. A CRF model is set as the baseline to compare the deep learning systems to a traditional machine learning approach. The same features are used for all the models.ResultsWe have obtained the best results with the Bidirectional LSTM-CRF model, which has outperformed all previously proposed systems. The specialized embeddings have helped to cover unusual words in DrugBank and MedLine, but not in the i2b2/VA dataset.ConclusionsWe present a state-of-the-art system for DNR and CCE. Automated word embeddings has allowed us to avoid costly feature engineering and achieve higher accuracy. Nevertheless, the embeddings need to be retrained over datasets that are adequate for the domain, in order to adequately cover the domain-specific vocabulary. 相似文献
7.
学术论文作者机构规范文档构建 总被引:2,自引:0,他引:2
以中国生物医学文献数据库为基础,面向基于学术论文开展机构检索、分析与评价相关知识服务需要,对学术论文作者机构名称规范目标与内容、体系结构与组织方式以及构建过程与实现策略进行研究、实践总结。 相似文献
8.
Thomas Bakken Seong Wook Kang Sunantha Kosonsiriluk Takehito Kuwayama Yupaporn Chaiseha Mohamed E. El Halawani 《Acta histochemica》2014
In the turkey, exogenous serotonin (5-hydroxytryptamine, 5-HT) increases prolactin (PRL) secretion by acting through the dopaminergic (DAergic) system. In the present study, infusion of the 5-HT2C receptor agonist, (R)(−)-DOI hydrochloride (DOI), into the third ventricle stimulates PRL secretion, whereas the 5-HT1A receptor agonist, (+/−)-8-OH-DPAT hydrobromide (DPAT), inhibits PRL secretion. Using the immediate-early gene, c-fos, as an indicator of neuronal activity, in situ hybridization histochemistry showed preferential c-fos co-localization within tyrosine hydroxylase immunoreactive neurons (the rate limiting enzyme in DA synthesis) in the areas of the nucleus preopticus medialis (POM) and the nucleus premammillaris (PMM), in response to DPAT and DOI, respectively. To clarify the involvement of 5-HT1A and 5-HT2C receptors in PRL regulation, their mRNA expression was determined on hypothalamic tissue sections from birds in different reproductive stages. A significant difference in 5-HT1A receptor was observed, with the POM of hypoprolactinemic short day and photorefractory birds showing the highest expression. 5-HT2C receptors mRNA did not change during the reproductive cycle. The data presented support the notion that DA neurons in the PMM and POM mediate the stimulatory and inhibitory effects of 5-HT, respectively, on PRL secretion and the 5-HTergic system can both stimulate and inhibit PRL secretion. 相似文献
9.
Yiming Chen Bruce E. Blough Kevin S. Murnane Clinton E. Canal 《Drug testing and analysis》2019,11(7):990-998
Synthetic cathinones (SCs) are β‐keto analogs of amphetamines. Like amphetamines, SCs target monoamine transporters; however, unusual neuropsychiatric symptoms have been associated with abuse of some SCs, suggesting SCs might possess additional pharmacological properties. We performed radioligand competition binding assays to assess the affinities of nine SCs at human 5‐HT2A receptors (5‐HT2AR) and muscarinic M1 receptors (M1R) transiently expressed in HEK293 cells. None of the SCs exhibited affinity at M1R (minimal displacement of [~Kd] [3H]scopolamine up to 10 μM). However, two SCs, α‐pyrrolidinopropiophenone (α‐PPP) and 4‐methyl‐α‐PPP, had low μM Ki values at 5‐HT2AR. In 5‐HT2AR–phosphoinositide hydrolysis assays, α‐PPP and 4‐methyl‐α‐PPP displayed inverse agonist activity. We further assessed the 5‐HT2AR functional activity of α‐PPP, and observed it competitively antagonized 5‐HT2AR signaling stimulated by the 5‐HT2R agonist (±)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI; Kb = 851 nM). To assess in vivo 5‐HT2AR activity, we examined the effects of α‐PPP on the DOI‐elicited head‐twitch response (HTR) in mice. α‐PPP dose‐dependently blocked the HTR with maximal suppression at 10 mg/kg (P < 0.0001), which is a moderate dose used in studies investigating psychostimulant properties of α‐PPP. To corroborate a 5‐HT2AR mechanism, we also tested 3,4‐methylenedioxy‐α‐PPP (MDPPP) and 3‐bromomethcathinone (3‐BMC), SCs that we observed had 5‐HT2AR Kis > 10 μM. Neither MDPPP nor 3‐BMC, at 10 mg/kg doses, attenuated the DOI HTR. Our results suggest α‐PPP has antagonist interactions at 5‐HT2AR in vitro that may translate at physiologically‐relevant doses in vivo. Considering 5‐HT2AR antagonism has been shown to mitigate effects of psychostimulants, this property may contribute to α‐PPPs unpopularity compared to other monoamine transporter inhibitors. 相似文献
10.