Based on previous species-specific studies, the intracallosal population could be classified as type 1, defined by a dense NADPH-d histochemical reaction (Yan et al. 1996); no type 2 neurons, characterized by low-level NADPH-d activity (Yan et al. 1996), were observed in the cc. Their dendritic trees and the morphology of the perikaryon enabled classification of NADPH-d+/NOSIP neurons into five groups: bipolar (fusiform, #HKI-272 mouse keyword# rectangular), round, polygonal (quadrangular), and pyramidal (triangular-pyriform). Our data therefore indicate that in the rat cc, as in the monkey

(Rockland and Nayyar 2012), there exists a wide neuronal heterogeneity that is actually based only on morphological criteria. The heterogeneity of NO-producing neurons in the cerebral cortex is based on different criteria. NADPH-d+/NOSIP neurons belong to one of two classes, type 1 or type 2 (Yan et al. 1996), based on their content in NO-producing Inhibitors,research,lifescience,medical enzymes. Moreover, nNOS–type 1 neurons display fast-spiking activity, they account for 0.5–2% of the cortical GABAergic population, and in these neurons nNOS is associated with somatostatin and neuropeptide Y (for a review see

Tricoire and Vitalis 2012). It Inhibitors,research,lifescience,medical cannot therefore be excluded that the NADPH-d/nNOS-type 1 neurons found in the rat cc are characterized by chemical heterogeneity. Further double-labeling studies are in progress in our laboratory to test this hypothesis. However, chemical heterogeneity has been Inhibitors,research,lifescience,medical observed in cc neurons, especially in the early stages of postnatal life; some intracallosal neurons contain calretinin, calbindin, GABA, and MAP2 (DeDiego et al. 1994; Riederer et al. 2004). Intracallosal neurons have a wide dendritic field with many dendrites extending into white matter. In the Inhibitors,research,lifescience,medical best cases, they could be followed up to layer VI of the overlying cerebral cortex; they may thus receive synaptic inputs from different sources. Collaterals of cortical afferent and efferent systems could terminate on these dendrites, a

hypothesis that is supported by previous studies. An anterograde tracer injected into different cortical areas anterogradely labeled synaptic terminals establishing synapses Florfenicol on white matter interstitial neurons (Clarke et al. 1993; Shering and Lowenstein 1994). Moreover, both thalamocortical and claustrocortical afferents, which form a dense plexus in layer VI (Zhang and Deschênes 1998; Arnold et al. 2001; Oda et al. 2004), could contact the dendrites of intracallosal neurons, which could thus receive a synaptic input also from neurons located in layer VI—whose axon is confined to the same layer—and/or from collaterals of corticothalamic axons (Briggs 2010). As intracallosal neurons are fully embedded in callosal fibers, another source of influence could be the callosal fibers themselves.

Although the estimates are misinformed, it is estimated that there are more than 15 million people around the world with rheumatic heart disease (RHD), the most severe sequel of RF. An estimated 300,000 new cases of RHD occur each year, and over 200,000 deaths caused by RHD each year [1]. The Brazilian public health system spent over 90 million U.S. dollars for treatment of RF and RHD patients. Furthermore, 31% of all Libraries cardiac surgeries in children are related to RF, which is also responsible Selleck Rigosertib for 7.5% mortality per year. Finally, it is estimated that

Brazil has over 10 million cases of throat infections caused by Streptococci that lead to 30,000 new cases of RF each year [2]. The M protein is the major virulence factor of GAS. The M protein involves bacterial adhesion, evasion, and promotes immune responses to GAS because of its immunogenicity [3]. It is composed of N and C-terminal portions; the N-terminal region is hypervariable and highly immunogenic whereas the C-terminal region Cyclopamine in vitro is highly conserved among the most GAS strains. The mechanisms leading to RF and RHD involve a cross-reaction between the N-terminal region of the alpha-helical coiled-coil M protein and self-proteins, mainly cardiac proteins. Accordingly, the

homology between the M protein and human proteins myosin, tropomyosin, keratin [4] and fibrillar collagen, the major component of heart valves [5], could be involved with the autoimmune response by the molecular mimicry mechanism [6], [7], [8], [9], [10] and [11]. In other words, the production of cross-reactive antibodies raised against GAS could be specifically within cardiac tissue, which would lead to an increased expression of the adhesion molecule VCAM-I [12] that facilitate the lymphocytic infiltration Resminostat through the

valve surface endothelium. This mechanism appears to be the initiating step for tissue damage and disease pathogenesis [12]. Both streptococcal primed CD4+ and CD8+ T lymphocytes are recruited probably under specific chemokine. This scenario might promote enhanced infiltration of mononuclear cells to the lesion and the production of inflammatory cytokines, such as IFN-γ and TNF-α, resulting in further tissue destruction and necrosis [12], [13] and [14]. The triggering of an autoimmune response involves antigenic presentation by macrophages via human leukocyte antigen-II (HLA-II) molecules to the T cell receptor. These molecules are genetically controlled and some alleles have already been described as being associated with the development of RF/RHD. Briefly, DR2 and DR4 were found in association with individuals in America; DR4, in Saudi Arabia; DR1 and DR6, in South Africa; DR7 and DR11, in Turkey; and DR7 and DR53, in Brazil. It is interesting to note that a DR7 defined molecular approach was also found in Latvians and Egyptians, and this was associated with the worsening of the valve damage [15].

More important, the solution to TRS is closely dependent on understanding the biology of schizophrenia in general. Meanwhile, the immediate treatment needs of TRS must be addressed with the available knowledge and tools. Treatment of TRS Verifying compliance by measuring neuroleptic plasma level or prolactin levels should be the starting point in the treatment of a TRS patient. Reconsidering doses and dosing should follow so that EPS

and akathisia are not confounded with TRS. Assessing and treating psychiatric comorbidities and medical comorbidities should follow. Nonpharmacological, Inhibitors,research,lifescience,medical social, family, and personal needs that might affect illness manifestation and nonresponse to treatment should be addressed.70-73 Realistic treatment targets, which consider the premorbid (often poor) functioning, should then

be set. It is essential to remember that in an illness that is by definition chronic, such as schizophrenia, response is a relative Inhibitors,research,lifescience,medical term and that many patients continue to suffer from low-level symptoms even after a significant response to treatment Inhibitors,research,lifescience,medical has Adriamycin occurred. Biological treatment for TRS patients is centered on the use of clozapine or newer atypical antipsychotics, augmentation drug therapies, and the combination of antipsychotics with electroconvulsive treatment (ECT). These strategics have been well reviewed elsewhere37,74,75 and thus will be briefly summarized here. However, before reviewing each individual intervention, it is essential to consider the inherent difficulties in conducting trials in TRS patients and hence providing good scientific data to address this prevalent problem. Trials in TRS patients are longer and more laborious, the Inhibitors,research,lifescience,medical population is difficult to Inhibitors,research,lifescience,medical agree upon and even more difficult to recruit. More importantly, when strategies in which

an active compound or placebo is added to an antipsychotic (adjunctive therapy or augmentation) are evaluated, the sample size necessary to obtain valid results is extremely large – a fact that further increases the effort and the cost of the trial.76 Moreover, due to pharmacokinetic interactions, add-on trials present difficulties in interpreting the results. It is often difficult to determine whether the advantage of the added compound is due to an intrinsic property of the added compound or due to changing the blood concentration of the concomitantly administered medication. Because of the difficulties conducting prospective trials much in TRS patients, clinicians often base their practice on consensus algorithms. Unfortunately, these algorithms are too often based on impressionistic data rather than on randomized clinical trials. Clozapine Despite some recent reservations, clozapine remains the gold standard for the treatment of TRS, being the only drug with proven superiority to both chlorpromazine in rigorously defined TRS19 and other classic neuroleptics.

Pendant la réalisation du bilan, le sport intense, même à l’entraînement, et éventuellement lors des activités scolaires, doit être contre-indiqué. Cette inhibitors contre-indication temporaire doit être consignée dans le dossier médical, clairement expliquée au sportif et si besoin à sa famille, et un certificat explicite doit lui être remis. Les EE sous-maximales, type tests

de Ruffier-Dickson ou du tabouret, qui ont une très faible valeur diagnostique, ne doivent plus être réalisées pour détecter des contre-indications cardiovasculaires à la pratique du sport. Les EE maximales réalisées en milieu cardiologique doivent être privilégiées. Cependant, elles ne doivent pas être systématiques mais ciblées, et leurs limites doivent être bien connues. Les trois principaux objectifs de l’EE sont de vérifier la normalité des adaptations cardiovasculaires à l’exercice, de quantifier la Autophagy inhibitor ic50 capacité fonctionnelle individuelle et de détecter une pathologie coronaire ou arythmique asymptomatique. L’EE est souvent aussi proposée pour vérifier la « normalisation » des particularités de l’ECG de repos de l’athlète. Les limites de l’EE doivent être bien connues

du praticien prescripteur et être clairement expliquées au sportif. En effet, cet examen ne doit pas être assimilé à une assurance tout risque. Ainsi, si l’EE détecte assez bien la maladie coronaire « installée », ayant un retentissement sur le débit coronaire à l’effort, sa valeur prédictive de survenue d’un BIBW2992 cell line accident aigu par érosion ou Oxalosuccinic acid rupture de plaque lipidique molle est très faible. La survenue d’un syndrome coronaire aigu chez un sportif, en règle générale vétéran, dans les mois qui suivent la réalisation d’une EE normale, n’est pas rare. De même, le pouvoir déclenchant et la reproductibilité de ce test pour les arythmies sont médiocres. Le sportif, surtout vétéran ou avec un risque cardiovasculaire significatif, bien informé doit

comprendre et accepter les limites de cet examen et consulter au moindre symptôme inhabituel même s’il a réalisé une EE classée « normale » récemment. De même, le sportif qui reprend une pratique sportive doit toujours accepter une reprise très progressive sur 6 à 8 semaines, quel que soit le résultat de l’EE. Les indications de l’EE doivent donc être ciblées et non systématiques. Les sportifs de haut niveau, inscrits sur les listes de leur fédération, doivent légalement avoir une EE, à visée diagnostique et non de suivi de l’entraînement, au moins tous les 4 ans. Chez tous les pratiquants, l’EE est nécessaire en cas de symptôme ou de pathologie cardiovasculaire connue (y compris l’hypertension artérielle) et dès qu’un doute clinique et/ou ECG plane sur l’intégrité de leur système cardiovasculaire. Nous avons vu qu’avant 35 ans, chez un sportif asymptomatique, l’EE n’était pas recommandée. En effet, dans cette population, la prévalence de la maladie coronaire est très faible et l’EE ne sera pas assez discriminante.

38 The pineal hormone melatonin often, but not always, shows a lower nocturnal peak in depressed patients. Cerebrospinal fluid hypocretin-1 levels have a low amplitude rhythm in controls which is even less in depression.39 Morning elevations of plasma IL-6 and a reversal of its circadian rhythm has been found in MDD patients, in the absence of hypercortisolism.40 These are but a few examples, that indicate alterations in circadian organization. The majority of results

are consistent with dampened diurnal variations Inhibitors,research,lifescience,medical in depression (diminished amplitude), and sometimes a phase advance, independent of whether the variable had a higher or lower mean value than controls. Only a few studies have attempted to look at. correlations with DV IL-6 levels correlated significantly with mood ratings.40 Depressed patients with evening mood improvements had smaller increases in regional cerebral metabolic

rate of glucose (rCMRglc) during evening relative to morning in lingual and fusiform cortices, midbrain reticular formation, and locus coeruleus Inhibitors,research,lifescience,medical and greater increases in rCMRglc in parietal and temporal cortices, compared with healthy subjects.41 Interestingly, Inhibitors,research,lifescience,medical evening mood improvements were associated with increased metabolic activity in ventral limbic-paralimbic, parietal, temporal, and frontal regions and in the cerebellum, ‘this increased metabolic pattern was considered to reflect partial normalization Inhibitors,research,lifescience,medical of primary and compensatory neural systems involved in affect, production and regulation.41 Another intriguing finding is that patients with high DV tended to show low circadian rhythmicity in skin body temperature, whereas patients with low DV tended toward a higher diurnal variation in skin body temperature.42 Again an indirect, reflection of lowered circadian amplitude permitting mood

variability to emerge? What is important? It is axiomatic (for a chronobiologist) that, stable timing between internal rhythms such as temperature and sleep with respect to the external day-night cycle is crucial for well-being. Inhibitors,research,lifescience,medical To establish stable phase relationships two characteristics are important: adequate second amplitude of the circadian pacemaker (a good endogenous rhythm), and adequate strength of the zeitgeber (good exogenous learn more 24-hour input signals). The scattered evidence suggest that it is these two characteristics that are disturbed in MDD. Internal rhythms are flatter – thus prone to desynchronization. The lowered strength of zeitgebers in depressive patients (whether social or light exposure) also permits rhythms to drift out of sync and show greater variability from day to day. That mood changes across the day is normal. DV is of itself not pathologic. However, DV research suggests that any misalignment of internal clock, sleep, and external light-dark cycle can induce mood changes, particularly in vulnerable individuals.

8. Theranostic Liposomes Simultaneous therapy and diagnosis following codelivery of therapeutic and imaging

agents, theranostic, are determinant for the development of personalized medicine since it would allow clinicians to detect and characterize lesions and ABT 199 rapidly evaluate tumor response and modify treatment accordingly (increase dose, stop treatment, or use an alternate Inhibitors,research,lifescience,medical drug) [377–379]. Indeed, liposomes are currently widely used for diagnosis (see recent reviews) [380–382]. Kenny et al. designed PEGylated liposome-entrapped siRNA nanoparticles (LEsiRNA) loaded with gadolinium (III) for magnetic resonance imaging, siRNA against the apoptosis inhibitor survivin for tumor therapy, and labeled with DOPE-rhodamine for fluorescence detection [383]. Accumulation of LEsiRNA in ovarian cancer xenografts after intravenous injection was demonstrated by MRI and confirmed

post mortem in tumor biopsies by fluorescence with in vivo survivin silencing and tumor weight reduction. Gd-labeled, doxorubicin-loaded Inhibitors,research,lifescience,medical thermo-responsive liposomes allowed detection of both tumor imaging by MRI and tumor regression after localized heating [384]. Note Inhibitors,research,lifescience,medical that to retain thermoresponsiveness after Gd-labeling a new Gd-chelate-dendron-based lipid was included in the lipid bilayer instead of a standard Gd-lipid conjugate to decrease Gd-lipid content to enhance thermosensitivity. The use of magnetic resonance imaging (MRI) to allow both tumor visualization and Inhibitors,research,lifescience,medical temperature feedback for imaging-guided thermo-responsive drug delivery showed improved therapy of the image-guided, thermallyinduced drug release [385, 386]. Labeling of prednisolone-labeled liposomes did not decrease its therapeutic activity, allowed evaluation of in vivo drug biodistribution and response monitoring simultaneously, with MRI signal detection 1 week after injection [387]. To combine the advantages of three imaging modalities (optical imaging, CT imaging,

and MRI), Li et al. and Mitchell et al. developed liposomes labeled with Inhibitors,research,lifescience,medical a fluorophore tracer, with 99mTc, 111In or 64Cu, and Gd [388, 389]. Since most facilities do not possess all the imaging equipment, this system would allow a more flexible followup of therapeutic activity by optical tuclazepam imaging, while in depth studies would use CT or MRI without the need of administration of another imaging agent. Spatially controlled thermallyinduced drug release was achieved with MRI-guided high intensity focused ultrasound heating of the targeted tumor region resulting in deep tumor penetration of doxorubicin-loaded thermo-sensitive liposomes, coloading of liposomes with doxorubicin and gadolinium allowing tumor visualization and therapy [385, 386, 390]. The contrast agent used for the preparation of theranostic siRNA liposomes must be chosen with care. Mikhaylova et al.

The completion of the human genome project,72 the parallel development of the HapMap database of human SNP variation, and the availability of information on more than 3.1 million SNPs across the human genome have paved the way to effectively carry out large-scale GWAS.73-75 Genetic association studies are based on the common disease common variant hypothesis. This hypothesis proposes that common diseases are a result of interactive contribution of common variants with small Inhibitors,research,lifescience,medical effect sizes, and the susceptibility alleles will be shared by a significant proportion

of unrelated affected individuals. This is the basis of both hypothesis-based candidate gene association studies as well as the hypothesis-free GWAS method. In the past 4 years at least 11 GWAS have attempted to identify susceptibility genes for schizophrenia by genotyping individual samples Inhibitors,research,lifescience,medical as well as using DNA poolingbased methods. GWAS using DNA pooling DNA pooling was initially proposed as a method to reduce genotyping costs in large-scale association studies.76 DNA from cases and controls are pooled into two separate groups, and the differences in allele frequency between the two groups are estimated to assess association. The first pooling-based association study was genecentric, and analyzed 25

494 SNPs present within 10 kb of each of a large set of genes77 (Table II). In the initial discovery sample a significant Inhibitors,research,lifescience,medical association of the marker rs752016 in Inhibitor Library molecular weight intron 11 of the Plexin A2 gene (PLXNA2, 1q32; OR = 1.49; P=0.006) was found. A similar association was observed in the replication Inhibitors,research,lifescience,medical case-control as well as family based samples. However, independent replications for this SNP have been mixed.78 – 80 Shifman et al81 conducted a pooling-based GWAS study and observed

female-specific association of the SNP rs7341475 G/A, in the fourth intron of the reelin gene (RELN, ORGG=2.1, 9.8×10-5). This was confirmed in a replication sample of patients of European ancestry from the United Kingdom, but not in samples from three other populations (Irish, Inhibitors,research,lifescience,medical tuclazepam American, and Chinese). The trend in the last three samples was in the same direction, and was significant in a meta-analysis including all samples ORGG=1.58 (1.31-1.89), P=8.8×10-7. However none of these observations were significant after correcting for multiple testing. The reelin protein is a serine protease that plays an important role in corticogenesis and it is associated with an autosomal recessive form of lissencephaly.82 It has also been implicated in neurotransmitter-related GSK3(3 signaling and regulation of NMDA receptor activation.83 Polymorphisms in the RELN gene have been associated with neurocognitive endophenotypes of schizophrenia (eg, working memory and executive functioning).84,85 Furthermore, the association of the RELN gene with schizophrenia has been replicated in an independent sample.

However, it has been informed that at higher concentrations could induce breast cancer cell apoptosis [36]. This is an ER independent and nongenomic effect; it was found in ER negative breast cancer cells and other cell types such as malignant gliomas, pancreatic carcinomas, and melanomas. On the other hand, estradiol has an antiapoptotic influence in both, ER positive and negative cells, in addition to its proliferative effect on ER positive cells; the antiapoptotic effect has also been reported in MCF-7 Inhibitors,research,lifescience,medical breast cancer cell line [37]. From the results obtained in cell cultures,

it might conclude that all the compositions containing 20mM of TMX showed an important cytotoxic effect. This phenomenon would be related with the induction of cellular apoptosis described above; the effect was also observed in ME N° 1 and 4 containing 10mM TMX. The % of viable cells observed

Inhibitors,research,lifescience,medical would indicate that seven of the fifteen assayed compositions were able to solubilize an enough amount of TMX capable to show a modification in the apoptosis cellular induction. It is also interesting to remark that this phenomenon is observed in presence of the above demonstrated proliferative effect of Inhibitors,research,lifescience,medical estradiol. It can be concluded that formulations 1 and 4 had the best in vitro performance because they were able to show an important antiproliferative effect even when they were loading the intermediate dose. Another interesting observation to point out is that formulation

3 showed the highest percentage of cell viability at any TMX concentration; this formula is the one which has the highest PC (16%) concentration. Previous reports showed that PC content is increased in cancer Inhibitors,research,lifescience,medical cells and have an important role in their proliferation [38, 39]. So, it is expected that this stimulation on cell proliferation can be attributed to the levels of PC. Inhibitors,research,lifescience,medical This observation and the mechanism described above suggest that the proposed MEs would present a high cellular uptake; anyway, PC proliferation effect has to Dichloromethane dehalogenase be considered in further pharmacotherapeutic evaluation. The obtained MEs are promising in the current state of increasing interest for nanocarriers that can be used for TMX delivery. For example, ABT-263 purchase Chawla and Amiji, examined biodegradable polymeric nanoparticles uptake and distribution in MCF-7 breast cancer cell line. They compared TMX intracellular concentration when delivered by the nanoparticles and in solution, and they found that the drug uptake from the nanoparticles followed a saturable transport. Therefore, above certain concentration, TMX intracellular concentration was much higher when delivered by the solution [1]. On the contrary, MEs designed in this work did not show signs of limited transport in none of the selected drug concentrations.

132 Turner et al133 recently predicted several possible miRNA binding sites within the GR first exon, suggesting further regulation of GR genes by miRNAs. TABLE I. miRNAs implicated in stress and depression. miRNAs in response to stress Several types of stressors have been utilized to examine how miRNAs respond to stressors. Interestingly, acute and chronic restrained stress cause differential changes in miRNA expression in a brain region-specific manner (Table I). 134 For example, acute stress Inhibitors,research,lifescience,medical induces a transient increase in the expression of

selected miRNAs (miR-9, miR-9*, miR-26b, miR-29b, miR-30b, miR-30c, miR-30e, miR-125a, miR-126-3p, miR-129-3p, miR-207, miR-212, miR-351, miR-423, miR-487b, miR-494, miR-690, miR691, miR-709, miR-711, and Let-7 a-e) in the frontal cortex, but not the hippocampus. Some of them (let-7a, miR-9, miR-26a/b, miR-30b/c, and miR-125a) show an increase in their expression Inhibitors,research,lifescience,medical 5 days after acute stress; however, their expression levels are not altered after repeated restraint. These results suggest that acute stress modulates miRNA expression quickly to external stimuli by changing their synaptic efficacy through regulation

of localized mRNA translation. Using psychological stress (acute or chronic immobilization), Meerson et al135 examined miRNA expression in the central amygdala and the Cornu Ammonis area 1 (CA1) region of the hippocampus of Inhibitors,research,lifescience,medical rats subjected to acute or chronic immobilization stress Inhibitors,research,lifescience,medical (Table I). They found that the expression of several miRNAs was differentially altered during acute and chronic stress, with chronic stress causing much larger changes than acute stress. Some of the miRNAs that were altered during acute and chronic stress include: miR-134, miR-183, miR-132, Let-7a-l, miR-9-1, and miR-124a-l. Interestingly, except for miR-Let-7a-l, the expression of stress-responsive miRNAs were different in the two analyzed brain regions. In the CA1 region, miR-376b

and miR-208 increased whereas miR-9-1 decreased Inhibitors,research,lifescience,medical under both acute and chronic stress conditions. Stressresponsive miR-134 and miR-183 target many Crenolanib manufacturer splicing factors, such as SC35, SRP46, and SFRSll. SC35 promotes the alternative splicing of acetylcholinesterase (AChE) from the synapse-associated isoform AChE-S to soluble AChE-R protein and the expression of SC35 is increased during stress. Thus, by regulating splicing factors and their nearly targets, miR-183 and miR-134 may modify both alternative splicing and cholinergic neurotransmission in the stressed brain. In addition, one of the targets of miR-183 is profilin 2 mRNA, which regulates dendritic spine morphology in neurons. Interestingly, neurotransmitter homeostasis and behavior are severely affected in profilin 2 knockdown mice136 and prolifin 2 (PFN2) expression is increased in lymphoblastoid cell lines of monozygotic twin pairs discordant for bipolar disorder.

In this respect, we show that

multivariate analyses can be used to remove contaminant behaviors. This strategy therefore measures the impact of stressors and/or antidepressants in animals that are genetically prone to display hypersensitivity to fear-related events. This is illustrated by our proposal that the socially stressed LEW is an appropriate model of posttraumatic stress disorder, whereas the WKY may prove important in future studies into the genetic basis of the hypersensitivity of central noradrenergic systems to stress and NA-related tricyclics. Our results in LEW also underline the need to use ethologically relevant models of stress, Inhibitors,research,lifescience,medical such as social stress, rather than aversive stressors without any clearcut relevance to humans (eg, electric shocks). The final series Inhibitors,research,lifescience,medical of experiments described above illustrate how a strategy

based on an initial screening of inbred rat strains applies to key Erlotinib cost neurochemical targets, such as the 5-HTT, thereby filling a gap in the animal models currently available for the study of the consequences of human allelic variations in 5-HTT. This survey was never intended to indicate that a comparison between inbred rat strains is the most valuable strategy, but rather to show that it Inhibitors,research,lifescience,medical is a valuable complement to currently existing models, most of which involve the use of transgenic strategics in mice. Selected abbreviations and acronyms [3H]8-OH-DPAT [3H]8-hydroxy-2-(di-n-propylamino)tetralin F344 Fischer 344 rat 5-HIAA 5-hydroxyindoleacetic acid HPA hypothalamo-pituitary-adrenal

(axis) 5-HT serotonin (5-hydroxytriptamine) 5-HTT serotonin transporter LEW Lewis Inhibitors,research,lifescience,medical rat NA noradrenaline SHR sponstaneously hypertensive rat SRRI selective serotonin reuptake inhibitor WKY Wistar-Kyoto rat Notes The author wishes to thank all the laboratory members who contributed to the work described: Dr A. Ramos for the behavioral SHR/LEW comparison; Dr O. Berton for the neurochemical comparisons SHR/LEW; Dr M. Durand for the psychoneuroendocrine SHR/WKY comparison; F. Pollier and Dr F. Fernandez for the studies comparing 5-HTT in different strains; and Dr V. Guyonnet-Dupérat Inhibitors,research,lifescience,medical and Dr M-P. Moisan for the molecular biology and molecular genetics experiments. Phosphoprotein phosphatase I also wish to thank S. Aguerre for her technical assistance. Prof Y. Michotte, Prof G. Ebinger, and Dr S. Sarre (Brussels, Belgium) for the microdialysis experiments, and Prof J-M. Launay (Paris, France) for his work on the platelet 5-HTT in F344 and LEW. Dr P. Mormède is thanked for his positive advice throughout the course of these experiments.
Modern psychopharmacology began in the 1950s with the discovery of chlorpromazine and later haloperidol, drugs that were mainly discovered by serendipity. A vast number of similar phenothiazinc- and butyrophe none-structured “me too” drugs with similar receptor binding profiles and therapeutic benefit, were developed in the subsequent years (the so-called typical antipsychotics).