班公湖带多不杂超大型富金斑岩铜矿床的成岩成矿年代学、岩石学及高氧化岩浆¬流体-成矿作用

Duobuza copper deposit, newly discovered typical gold-rich porphyry copper deposit with superlarge potential, is located in the Tiegelong Mesozoic tectonic -magmatic arc of the southern edge of Qiangtang block and the northern margin of Bangonghu-Nujiang suture. Quartz diorite porphyrite and grandiorite porphyry, occurred in stock, are the main ore-bearing porphyries. As the emplacement of porphyry stock, a wide range of hydrothermal alteration has developed. Within the framework of the ore district, abundant hydrothermal magnetite developed, and the relationship between precipitation of copper and gold and hydrothermal magnetite seems much close. Correspondingly, a series of veinlets and network veinlets occurred in all alteration zones. Therefore, systematic research on such a superlarge high-grade Duobuza gold-rich porphyry copper deposit can fully revealed the metallogenic characteristics of gold-rich porphyry copper deposits in this region, establish metallogenetic model and prospecting criteria, and has important practical significance on the promotion of regional exploration. In addition, this research on it can enrich metallogenic theory of strong oxidation magma-fluid to gold-rich porphyry copper deposit, and will be helpful to understand the metallogenic characteristics in early of subduction of Gangdese arc stages and its entire evolution history of the Qinghai-Tibet Plateau, the temporal and spatial distribution of ore deposits and their geodynamics settings. Northern ore body of Duobuza copper deposit have been controlled with width (north-south) about 100 ~ 400 m, length (east-west) about 1400 m, dip of 200 °, angle of dip 65 °~ 80 °. And controlled resource amount is of 2.7 million tons Cu with grade 0.94% and 13 tons Au with 0.21g/tAu. Overall features of ore body are large scale, higher grade copper, gold-rich. Ore occurred in the body of granodiotite porphyry and quartz diorite porphyrite and its contact zone with wall rock. Through the detailed mapping and field work studies, some typies of alteration are identificated as follows: albitization, biotititation, sericitization, silication, epidotization, chloritization, carbonatization, illitization, kaolinization and so on. The range of alteration is more than 10km2. Wall alteration zone can be divided into potassic alteration, moderate argillization alteration, argillization, illite-hydromuscovite or propylitization from ore-bearing porphyry center outwards, but phyllic alteration has not well developed and only sericite-quartz veins occurred in local area. Moreover, micro-fracture is development in ore district , and correspondingly a series of veinlets are development as follows: biotite vein (EB type), K-feldspar-biotite-chalcopyrite-quartz vein, magnetite-antinolite-K-feldspar vein, quartz-chalcopyrite-magnetite veins (A-type), quartz-magnetite-biotite-K-feldspar vein, chalcopyrite veinlets in potassic alteration zone; (2) chalcopyrite occurring in the center vein–quartz vein (B type), chalcopyrite veinlets, chalcopyrite-gypsum vein in intermediate argillization alteration; (3) chalcopyrite- pyrite-quartz vein, pyrite-quartz vein, chalcopyrite-gypsum veins, quartz-gypsum- molybdenite-chalcopyrite vein in argillization alteration; (4) gypsum veins, quartz-(molybdenite)-chalcopyrite vein, quartz-pyrite vein, gypsum- chalcopyrite vein, potassium feldspar veinlets, Carbonate veins, quartz-magnetite veins in the wall rock. In short, various veins are very abundant within the framework of the ore district. The results of electronic probe microscopy analysis (EMPA) indicate that Albite (Ab 91.5~99.7%) occurred along the rim of plagioclase phenocryst and fracture, and respresents the earliest stages of alteration. K-feldspar (Or 75.1~96.9%) altered plagioclase phenocryst and matrix or formed secondary potassium feldspar veinlets. Secondary biotite occurred mainly in phenocryst, matrix and veinlets, belong to magnesium-rich biotite formed under the conditions of high-oxidation magma- hydrothermal. Chloritization developed in all alteration zones and alterd iron- magnesium minerals such as biotite and hornblende and then formed chlorite veinlets. As the temperature rises, Si in the tetrahedral site of chlorite decreased, and chlorite component evolved from diabantite to ripiolite. The consistent 280℃~360℃ of formation temperature hinted that chlorite formed on the same temperature range in all alteration zones. However, formation temperature range of chlorite from the gypsum-carbonate-chlorite vein was 190℃~220℃, and it may be the product of the latest stage of hydrothermal activity. The closely relationship between biotite and rutile indicate that most of rutiles are precipitated in the process of biotite alteration and recrystallization. In addition, the V2O3 concentration of rutile from ore body in Duobuza gold-rich porphyry copper deposit is >0.4％, indicate that V concentration in rutile has important significance on marking main ore body of porphyry copper deposit. Apatites from Duobuza deposit all are F-rich. And apatite in the wall rock contained low MnO content and relatively high FeO content, which may due to the basaltic composition of the wall rocks. The MnO in apatite from altered porphyry show a strong positive correlation with FeO. In addition, Cl/F ratio of apatite from wall rock was highest, followed by the potassic alteration zone and potassic alteration zone overprinted by moderate argillization alteration was the lowest. SO2 in Apatite are in the scope of 0 to 0.66%, biotite in the apatite has the highest SO2, followed by the potassic alteration zone, potassic alteration zone overprinted by moderate argillization alteration, and the lowest in the surrounding rocks, which may be caused by the decrease of oxygen fugacity of hydrothermal fluid and S exhaust by sulfide precipitation in potassic alteration. Magnetite in the wall rock have higher Cr2O3 and lower Al2O3 features compared with altered porphyry, this may be due to basalt wall rock generally has high Cr content. And magnetites have higher TiO2 content in potassic alteration than moderate argillization alteration overprinted by potassic alteration, argillization and wall rock, suggested that its formation temperature in potassic alteration was the highest among them. The ore minerals mainly are chalcopyrite and bornite, and Au contents of chalcopyrite, bornite, and pyrite are similar with chalcopyrite slightly higher. The Eu* negative anomaly of disseminated chalcopyrite was relatively lower than chalcopyrite in veinlets. Within a drill hole, the Eu* negative anomaly of disseminated chalcopyrite was gradually larger from bottom to top. Magnetite has the same distribution model, with obvious negative Eu* abnormal, and ΣREE in great changes. The gypsum has the highest ΣREE content and the obvious negative anomaly, and biotite obviously has the Eu* abnormal. Based on the petrographic and geochemical characteristics, five series of magmatic rocks can be broadly classified; they are volcanic rocks of the normal island arc, high-Nb basaltic rocks, adakites, altered porphyry and diorite. The Sr, Nd, Hf isotopes and geochemistry of various series of magmatic rock show that they may be the result of mixing between basic magma and various degrees of acid magma coming from lower crust melted by high temperature basic underplating from partial melting of the subduction sediment melt metasomatic mantle wedge. Furthermore S isotope and Pb isotope of the sulfide, ore-bearing porphyries and volcanic rocks indicated ore-forming source is the mantle wedge metasomatied by subduction sediment melt. Oxygen fugacity of magma estimated by Fe2O3/FeO of whole rock and zircon Ce4+/Ce3+ indicated that the oxidation of basalt-andesitic rocks is higher than ore-forming porphyry, and might imply high-oxidation characteristics of underplated basic magma. Its high oxidative mechanism is likely mantle sources metasomatied by subduction sediment magma, including water and Fe3+. And such high oxidation of basaltic magma is conducive to the mantle of sulfides in the effective access to melt. And the An component of dark part within plagioclase phenocryst zoning belong to bytownite (An 74%), and its may be a result of magma composition changes refreshment by basaltic magma injection. SHRIMP zircon U-Pb and LA-ICP-MS zircon U-Pb geochronology study showed that the intrusions and volcanic rocks from Duobuza porphyry copper deposit belong to early Cretaceous magma series (126~105Ma). The magma evolution series are as follows: the earliest diorite and diorite porphyrite → ore-bearing porphyry and barren grandiorite porphyry →basaltic andesite → diorite porphyrite → andesite → basaltic andesite, and magma component shows a evolution trend from intermediate to intermediate-acid to basic. Based on the field evidences, the formation age of high-Nb basalt may be the latest. The Ar-Ar geochronology of altered secondary biotite, K-feldspar and sericite shows that the main mineralization lasting a interval of about 4 Ma, the duration limit of whole magma-hydrothermal evolution of about 6 Ma, and possibly such a long duration limit may result in the formation of Duobuza super-large copper deposit. Moreover, tectonic diagram and trace element geochemistry of volcanic rocks and diorite from Duobuza porphyry copper deposit confirm that it formed in a continental margin arc environment. Zircon U-Pb age of volcanic rocks and porphyry fall in the range of 105~121Ma, and Duobuza porphyry copper deposit locating in the north of the Bangonghu- Nujiang suture zone, suggested that Neo-Tethys ocean still subducted northward at least early Cretaceous, and its closure time should be later than 105 Ma. Three major inclusion types and ten subtypes are distinguished from quartz phenocrysts and various quartz veins. Vapor generally coexisting with brine inclusions, suggest that fluid boiling may be the main ore-forming mechanism. Raman spectrums of fluid inclusions display that the content of vapor and liquid inclusion mainly contain water, and vapor occasionally contain a little CO2. In addition, the component of liquid inclusions mainly include Cl-, SO42-, Na+, K+, a small amount of Ca2+, F-; and Cl- and Na+ show good correlation. Vapor mainly contains water, a small amount of CO2, CH4 and C2H6 and so on. The daughter minerals identified by Laman spectroscopy and SEM include gypsum, chalcopyrite, halite, sylvite, rutile, potassium feldspar, Fe-Mn-chloride and other minerals, and ore-forming fluid belong to a complex hydrothermal system containing H2O-NaCl-KClFeCl2CaCl2. H and O isotopic analysis of quartz phenocryst, vein quartz, magnetite, chlorite and gypsum from all alteration zones show that the ore-forming fluid of Duobuza gold-rich porphyry copper deposit consisted mainly of magmatic water, without addition of meteric water. Duobuza gold-rich porphyry copper deposit formed by the primary magmatic fluid (600-950C), which has high oxidation, ultra-high salinity and metallogenic element-rich, exsolution direct from the magma, and it is representative of the typical orthomagmatic end member of the porphyry continuum. Moreover, the fluid evolution model of Duobuza gold-rich porphyry copper deposit has been established. Furthermore, two key factors for formation of large Au-rich porphyry copper deposit have been summed up, which are ore-forming fluids earlier separated from magma and high oxidation magma-mineralization fluid system.

东北四海龙湾玛珥湖啊1500年来长链烯酮不饱和度温标与古水温重建

The alkenone unsaturation paleothermometer is an important proxy to reconstruct water temperature, and is widely applied to reconstructing sea surface temperature in most oceanographic settings. Recent research indicates that long chain alkenone is preserved in lacustrine sediments, and the alkenone unsaturation has good relationship with mean annual temperature in studied lakes. Thus, the alkenone unsaturation could be used as a temperature proxy to reconstruct temperature in limnic systems. In this study, we analyzed long chain alkenone from the varved sediments in Lake Sihailongwan, northeastern China. Based on the counting varves, we established time scale during the past 1500 years. The distribution pattern in the sediment is similar with the previous study in lacustrine environment. The ratio of C37:4 methyl ketone to the sum of C37 alkenones is high. Based on the published temperature- alkenone unsaturation equation, we reconstructed the mean air temperature and July water temperature during the past 1500 years. Three major cold periods are in AD560-950, AD 1540-1600 and AD1800-1920. Three major warm periods are AD450-550, AD 950-1400 and AD 1600-1800. The Medieval Warm Period was a significant warm periods. However, the traditional “Little Ice Age” was not a persistent cold period, and interrupted by relative longer warm period. The temperature variations in this study show a general similar pattern with the summer temperature reconstruction from Shihua Cave and the winter temperature from historical documents. The temperature variations from long chain alknone record show a good agreement with solar activity (10Be data from ice core and sunspot number from tree rings). It may suggest that solar activity is most important forcing in the studied area.

中-新元古代海洋的硫和碳同位素的演化

Data on seawater carbon isotope in the Mesoproterozoic and Neoproterozoic is abundant. However, the sulfur isotopic age curve of seawater sulfates determined through the analysis of sulfur isotopic composition of marine evaporite is uncertain in the Mesoproterozoic and Neoproterozoic since evaporites are generally rare in Precambrian. The Mesoproterozoic and Neoproterozoic Carbonate Formations preserve not only the carbon isotopic records, but also the sulfur isotopic records of coeval seawater in the Huabei Platform and the Yangtze Platform, China. Sulfur isotopic composition can be determined by the extraction of trace sulfate from carbonate samples. Successive measurements of sulfur and carbon isotopic compositions of carbonate samples from the Mesoproterozoic and Neoproterozoic strata in the Huabei Platform and the Yangtze Platform was accomplished through the extracting of trace sulfate from carbonates. Sulfur and carbon isotopic compositions of coeval seawater were obtained from analytical results of sulfur and carbon isotopes of the same sample without diagenetic alteration. The high-resolution age curve of sulfur isotope given in this paper may reflect the trend of variations in sulfur isotope composition of seawater sulfates during the Mesoproterozoic and Neoproterozoic. It can be correlated with the characteristics of variation in age curve of carbon isotope of coeval seawater carbonates. The δ34S values of seawater varied from +10.3-37.0‰ during the Mesoproterozoic, which took on oscillated variation on the whole. The δ34S values took on high values in the Mesoproterozoic Chuanlinggou stage, Tuanshanzi stage Tieling stage and in Neoproterozoic Jing'eryu stage. The average of those was about +30‰. The sulfates have low δ34S values in the Mesoproterozoic Yangzhuang stage and Hongshuizhuang stage, The average of those was all lower than +20‰. There occured large-amplitude changs in δ34S values of seawater during the Mesoproterozoic. Large-amplitude oscillate of 534S values occured in the intervals of 1600~1400Ma and 1300~1200Ma. The δ13C values of seawater are mostly negative in Changcheng stage of late Paleoproterozoic, -0 ± 1‰ range in Jixian stage of Mesoproterozoic , and the positive 2±2‰ commonly in early Neoproterozoic Jing'eryu stage. From 1000 Ma to 900 Ma, about 108 years interval of oceanic 513C record is shortage. At the end of Paleoproterozoic (1700 - 1600 Ma), the oceanic 813C values change from -3‰ to 0‰, but strongly oscillate near 1600 Ma. Two larger variations of seawater 513C values occur in the Mesoproterozoic: one is a cycle of about 4%o happens at ca. 1400 Ma; another is rise from >2‰ to>5‰ at ca. 1250 Ma and then become stable at the near 1000 Ma. There appears a large positive excursion over +20‰ in 534S value of ancient seawater sulfates in the early Doushantuo stage. Simultaneously, 8 C values of ancient seawater occur a positive excursion reaching 10‰. These allow δ4S values and 513C values to reach high values of+51.7‰ and +6.9‰, respectively. The range of variation in 834S values of seawater is relatively narrow and 513C values are quite high in the middle Doushantuo stage. Then, δ34S values of seawater become oscillating, the same happens in δ13C values. Negative excursions in 834S values and 813C values occur simultaneously at the end of the Doushantuo stage, and the minimum of δ34S values and δ13C values dropped to -11.3‰ and -5.7‰, respectively. The ancient seawater in the Dengying stage has high δS values and δ13C values. Most of the δ34S values of the trace sulfate samples varied between +23.6‰ and +37.9‰ except two boundaries of the Dengying Formation, and the S13C values of the carbonate samples of the Dengying Formation varied between +0.5‰ and +5.0‰. There appeared large negative excursion in 834S values and δ13C values of ancient seawater at the bounder of Precambrian-Cambrian. The isotopic characteristics of sulfur and carbon implicated that the organic productivity and isotopic fractionation caused by biology were low and the palaeoceanic environment was quite unstable during the Mesoproterozoic. The increase and subsequent oscillation of seawater δ13C value occurred from 1700 to 1600 Ma and near 1300 Ma may be responsible to the two global tectonic events happened at coeval time. The characteristics of variation in sulfur and carbon isotopes of ancient seawater imply strong changes in oceanic environment, which became beneficial to inhabitation and propagation of organism. The organic production and the burial rate of organic carbon once reached a quite high level during the Doushantuo stage. However, the state of environment became unstable that means the global climate and the environment possibly were fluctuating and reiterating after the global glaciation. The negative excursions of S34S values and δ13C values occurring at the end of the Doushantuo stage represent a global event, which might be relative to the oxidation of deep seawater. The isotopic characteristics of sulfur and carbon implicated that there were a high organic productivity and a high burial rate of organic carbon in the Dengying stage. It is obvious that the palaeoceanic environment in Dengying stage was stable corresponding and beneficial for biology to inhabit and propagate except for the two boundaries. The tendency of sulfur and carbon isotopic variations maybe resulted from the gradual oxygenation of ocean environment during the Dengying stage. It has been reported that the secular variations of the sulfur isotopic compositions in seawater was negative correlated with that of carbon isotopic compositions. However, our results show that it is not the case. They were negatively correlated in some intervals and positively in some other intervals of the Mesoproterozoic and Neoproterozoic. The difference in correlation may be associated with the changes in conditions of redox in oceanic environment, e.g. sharp change of the oxidation-reduction interface. The strong changes in global environment may induce the abnormality to occur in the biogeo chemical S and C cycles in the ocean and accordingly sharp Variations in isotopic composition of seawater sulfur and carbon during the Mesoproterozoic and Neoproterozoic. Simultaneously, the global tectonism caused large changes of 87Sr/86Sr ratios. The leading factor that causes the variation in isotopic composition is different in the different intervals of the Mesoproterozoic and Neoproterozoic. Thus, there may exist different models of the biogeochemical S and C cycles in the ocean during the Mesoproterozoic and Neoproterozoic.

西南土法炼锌导致的环境重金属污染研究

本文以我国西南的土法炼锌为例，较为系统的研究了锌矿冶炼导致的环境重金属污染问题。研究表明，土法炼锌使用硫化矿和使用氧化矿冶炼Cd通过大气的释放因子分别为1400 g/t和1200 g/t，Pb的释放因子分别为37000 g/t和25000 g/t，远高于国外相同行业相应污染物的释放因子。 土法炼锌活动造成了土壤和农作物严重的重金属污染。通过土壤中重金属的Zn/Cd和Pb/Cd比值，可以对炼锌烟尘沉降来源与冶炼废渣释放来源的重金属进行区分。污染土壤的Pb同位素组成特征证实土壤中的重金属主要来自于土法炼锌的释放。玉米不同器官中的Pb同位素比值表明，玉米根和茎中的Pb主要是来自土壤，而叶和果实中的Pb则主要来自大气中Pb的沉降。 对草海重金属污染研究结果显示，草海沉积物受到了Cd、Pb和Zn的严重污染。沉积物中的重金属主要以有机质结合态和残渣态形式存在。Pb同位素数据表明草海湖沉积物中重金属污染主要来自于土法炼锌的释放，同时其它来源Pb（例如汽车尾气的排放）对草海沉积物中的Pb也有一定贡献。草海沉积物重金属污染导致草海水生动植物体内重金属呈现不同程度的富积，部分鱼类体内Cd、Pb含量已超过国家食品卫生限量标准。

高强度瓷绝缘子的矿物组成和显微结构研究

以矿物学理论为基础，采用XRD、AAS、TEM和OM等分析仪器，对国产70kN、日本120kN和210kN高强度瓷绝缘子的化学成分、显微结构等特征进行了分析，找出造成国内外瓷绝缘子性能差异的主要因素。并对贵州地区的高强瓷非金属矿物原料进行了较系统的矿物学研究，确定了6个主要原料基地。在以上研究的基础上，优化设计了420kN和300kN高强度瓷绝缘子的配方及相关生产工艺。并对烧结出420kN高强度瓷绝缘子的化学成分与显微结构进行了研究分析。得到的主要结论如下： （1）对比国内外高强瓷得出，造成国内高强瓷性能差的主要因素是化学成分和显微结构。国内70kN样品含有较高的K2O和TiO2，严重超过了高强瓷标准配方值，而国外配方恰好落在标准值范围内；国内70kN样品晶相含量仅为35%，而国外210kN样品的晶相含量为48%，且晶粒细小分布均匀，玻璃相和气孔相含量也比国内产品少且分布均匀。 （2）采用XRD对贵州地区矿物原料进行分析，最终选定了毕节、大方6个高强瓷原材料产地。这些基地粘土类矿物原料，具有可塑性好，有害矿物含量少，化学成分中Si、Al比适中，Fe、Ti等杂质元素含量低的特点；铝氧类矿物具有含Al2O3含量高且杂质元素少的特点，是制备高强度瓷绝缘子的优质原料。 （3）在主要使用贵州所产的矿物原料基础上，结合国内外高强瓷的性能差异，优化设计了300kN和420kN高强瓷的配方和工艺。其中将坯料的颗粒度组成设定在：≥5µm43-48%，≥10µm25-31%，≥20µm5-12%，并采用合理烧结制度下烧结出420kN高强瓷，其烧结温度范围在13001400℃，最终产品通过IEC检测且显微结构较好。

I Cannot Tell: Edward Thomas's Uncertainties

Poster, Jeremy, 'I Cannot Tell: Edward Thomas's Uncertainties', In: 'Branch-Lines: Edward Thomas and Contemporary Poetry', Guy Cuthbertson & Lucy Newlyn (eds), (London: Enitharmon Press), pp.264, 2007 RAE2008

Keats and the Holocaust: Notes towards a post-temporalism

Grovier, Kelly, 'Keats and the Holocaust: Notes towards a post-temporalism', Literature and Theology (2003) 17 (4) pp.361-373 RAE2008

Recovering a lost inheritance : The marital economy and its absence from the Prehistory of Economics in Britain

Roberts, Michael. 'Recovering a lost inheritance: the marital economy and its absence from the Prehistory of Economics in Britain', in: 'The Marital Economy in Scandinavia and Britain 1400-1900', (Eds) Argen, Maria., Erickson, Amy Louise., Farnham: Ashgate, 2005, pp.239-256 RAE2008

Bequests and Burials : Changing Attitudes of the Laity as Patrons of English and Welsh Monasteries

St?ber, K. (2007). Bequests and Burials: Changing Attitudes of the Laity as Patrons of English and Welsh Monasteries. In E. Jamroziak and J. Burton (Eds.), Religious and Laity in Western Europe, 1000-1400: Interaction, negotiation, and power (pp.131-146). Turnhout: Brepols. RAE2008

Large-Amplitude nonlinear stability results for atmospheric circulations

Douglas, Robert; Cullen, M.J.P., (2002) 'Large-Amplitude nonlinear stability results for atmospheric circulations', The Quarterly Journal of the Royal Meteorological Society 129 pp.1969-1988 RAE2008

The Ornstein-Uhlenbeck semigroup in exterior domains

Wood, Ian; Geissert, M.; Heck, H.; Hieber, M., (2005) 'The Ornstein-Uhlenbeck semigroup in exterior domains', Archiv der Mathematik 86 pp.554-562 RAE2008

Soil differentiation using fingerprint Fourier transform infrared spectroscopy, chemometrics and genetic algorithm-based feature selection

Elliott, G. N., Worgan, H., Broadhurst, D. I., Draper, J. H., Scullion, J. (2007). Soil differentiation using fingerprint Fourier transform infrared spectroscopy, chemometrics and genetic algorithm-based feature selection. Soil Biology & Biochemistry, 39 (11), 2888-2896. Sponsorship: BBSRC / NERC RAE2008

Re-focusing risk assessment in forensic mental health nursing.

Editorial in the Journal of Psychiatric and Mental Health Nursing, 2015, 22(7)

Avaliação da qualidade de serviço

Dissertação de Mestrado apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Gestão da Qualidade.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.