Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

Unlike some other reproductions of classic texts (1) We have not used OCR(Optical Character Recognition), as this leads to bad quality books with introduced typos. (2) In books where there are images such as portraits, maps, sketches etc We have endeavoured to keep the quality of these images, so they represent accurately the original artefact. Although occasionally there may be certain imperfections with these old texts, we feel they deserve to be made available for future generations to enjoy.

The lymphatic system develops and functions in parallel with the blood circulatory system (termed the "hemovasculature") and accomplishes transport of interstitial fluids, dietary lipids, and reverse transport of cholesterol, immune cells, and antigens-providing a critical homeostatic fluid balance and transmission of immune cells and mediators back to the cardiovascular system. Although the daily flow of lymph (normally 1-2 L/day under unstressed conditions) is far lower than that of daily blood flow (which is 7,500 L/day), without the adequate functioning of the lymphatics, virtually all organs and tissues would acutely suffer many different physical and inflammatory stresses ranging from edema to organ system failure. Although blood and lymphatic vessels often form in anatomic parallels to one another, our knowledge of the workings of the lymphatic system, the fine structure of lymphatic networks, how they function in different organs, and how they are regulated physiologically and immunologically are far from parallel; our knowledge of the lymphatic system still remains at only a tiny fraction of what is understood about the cardiovascular system. Although both the cardiovascular and lymphatic systems are important transport systems, what they transport and how they transport and propel these very different cargoes could not be more dissimilar. This book provides an overview of the history of the discovery (and re-discovery) of the components of the lymphatic system, lymphatic anatomy, physiological functions of lymphatics, molecular features of the lymphatic system, and clinical perspectives involving lymphatics which may be of interest to scientists, clinicians, patients, and the lay public. We provide a current understanding of some of the more important structural similarities and differences between lymphatics and the blood vascular system, their coordinated control by angiogenic and hemangiogenic growth factors and other modulators, the fate and lineage determinants which control lymphatic development, and the roles that lymphatics may play in several different diseases.

Like so many of us, twenty-four year old Michael is tired of his monotonous existence. Then one morning he awakens in an abandoned alleyway; covered in blood and completely naked. After a narrow escape from authorities he is captured and imprisoned by a mysterious group who seem to possess unusual powers. Suddenly life is anything but boring. While learning to develop and utilize mind blowing, incredible abilities he is plunged into an unbelievable but very real adventure with evil incarnate. Like a great puzzle, pieces of a grand design begin to fit and Michael must accept truth and dismiss fiction as he discovers an ancient prophecy that threatens all life on this planet and how this threat directly relates to him. He must understand that he has a part to play in the events that have already been set in motion in the first installment of this ultimate theme of good versus evil.

Itisabundantlyclearthattheendocannabinoidsignallingsystemisubiquitously expressedthroughouttheanimalkingdomfromsimpleinvertebratestoman,and thatitisrepresentedinalmosteverycelltype. Thecomponentsofthesysteminrelationtothesynthesisandmetabolismofthe endocannabinoidsandtheirbiologicaltargetsarebeginningtobeunravelled,but the degree of complexity involved is enormous. This is particularly true for endocannabinoidsignallinginthecentralnervoussystem,whichisthesubjectof thisvolume. Inthebook,avarietyofauthors,whoareallveryactiveresearchersinthe?eld, providecurrentaccountsoftherolesoftheendocannabinoidsysteminnormalbrain physiologyinrelationtotheneurobiologyofessentialbehaviorsandinanumberof centraldiseasestates. The?rstpartprovidesabackgroundand"toolbox",detailingwhatisknown abouttheendocannabinoidsthemselvesandtheirtargetreceptorsandhowthey in?uencesynapticactivity. Itgoesontodescribethegeneticandpharmacological methodsavailableforinvestigatingthesystem. The second part describes endocannabinoid roles in key systems controlling appetite,pain,memoryandlearning,stressresponsesandreproduction. The?nalgroupofchaptersreviewsthecurrentstateofknowledgesurrounding thefunctionoftheendocannabinoidsystemindepression,drugaddiction,schi- phrenia,feedingdisordersandTourette'ssyndrome. Giventheenormousamountofinformationavailableandtherateofprogressin research,itisimpossibleforthevolumetobetotallycomprehensive,butwetrust thatitwillprovideanexcellentbackgroundtoresearcherswantingtoexpandtheir areaofinterestandtonewcomerstothe?eld. Nottingham,UnitedKingdom DavidKendall StephenAlexander v Contents PartI Biochemistry,Pharmacology,GeneticsandChemistry 1 TheLifeCycleoftheEndocannabinoids:Formation andInactivation...3 StephenP. H. AlexanderandDavidA. Kendall 2 EndocannabinoidReceptorPharmacology ...37 KenMackieandBettyYao 3 EndocannabinoidReceptors:CNSLocalizationoftheCB 1 CannabinoidReceptor...65 Istva'nKatona 4 PharmacologicalToolsinEndocannabinoidNeurobiology...87 MarcoMorandAlessioLodola 5 GeneticModelsoftheEndocannabinoidSystem ...111 KrisztinaMonoryandBeatLutz 6 EndocannabinoidSignalinginNeuralPlasticity ...141 BradleyE. Alger 7 LessonsfromNonmammalianSpecies ...173 KenSoderstrom PartII PhysiologyandPathophysiology 8 RolesoftheEndocannabinoidSysteminLearning andMemory ...201 GiovanniMarsicanoandPaulineLafenetre vii viii Contents 9 EndocannabinoidsandtheNon-HomeostaticControl ofAppetite ...231 TimC. Kirkham 10 Cannabinoid/EndocannabinoidSignalingImpactonEarly PregnancyEvents...255 XiaofeiSunandSudhansuK. Dey 11 TargetingtheCannabinoidSystemtoProduceAnalgesia ...275 DeviRaniSagar,MaulikJhaveri,andVictoriaChapman 12 IntegrationofEndocannabinoidSignalingintotheNeural NetworkRegulatingStress-InducedActivationofthe Hypothalamic-Pituitary-AdrenalAxis ...289 BorisB. GorzalkaandMatthewN. Hill PartIII Pathology 13 DrugAddiction ...309 ZuzanaJustinova,LeighV. Panlilio,andStevenR. Goldberg 14 RoleofEndocannabinoidSignalinginAnxietyandDepression...347 SachinPatelandCeciliaJ. Hillard 15 FeedingDisordersandObesity...373 CristinaCervino,ValentinaVicennati,RenatoPasquali, andUbertoPagotto 16 Schizophrenia...387 F. Markus 17 Tourette'sSyndrome...397 KirstenR. Mu..ller-Vahl Index ...411 Contributors StephenP. H. Alexander SchoolofBiomedicalSciencesandInstituteofNeuroscience,UniversityofN- tingham Medical School, Queens Medical Centre, Nottingham NG7 2UH, UK; steve. alexander@nottingham. ac. uk BradleyE. Alger Departments of Physiology and Psychiatry, University of Maryland School of Medicine, 655 W. Baltimore St. /BRB 5-025, Baltimore, MD 21201, USA; balger@umaryland. edu CristinaCervino Endocrinology Unit and Center of Applied Biomedical Research (C. R. B. A. ), DepartmentofInternalMedicineandGastroenterology,S. Orsola-MalpighiHos- tal,AlmaMaterStudiorumUniversityofBologna,40138Bologna,Italy VictoriaChapman SchoolofBiomedicalSciences,UniversityofNottingham,NottinghamNG72UH, UK;victoria. chapman@nottingham. ac. uk SudhansuK. Dey Departments of Pharmacology, Pediatrics and Cell & Developmental Biology, Division of Reproductive and Developmental Biology, Vanderbilt University MedicalCenter,Nashville,TN37232,USA;sk. dey@vanderbilt. edu StevenR.

This thoroughly updated edition covers all clinical aspects of neuroinflammation. The latest developments in pathogenesis and advances in treatment are provided, along with an understanding of the immune system's role and interactions between the activated immune cells, cerebral endothelial cells, and other main components of the immune cascade. Cutting-edge and authoritative, this volume offers practitioners a valuable resource for research and clinical practice.

An integrated reference which could form the basis for advanced courses on development or become a resource for individuals teaching basic courses. Following an introduction by the volume editors, the 11 chapters represent 11 different systems, arranged phylogenetically, beginning with prokaryotic s

Itisabundantlyclearthattheendocannabinoidsignallingsystemisubiquitously expressedthroughouttheanimalkingdomfromsimpleinvertebratestoman,and thatitisrepresentedinalmosteverycelltype. Thecomponentsofthesysteminrelationtothesynthesisandmetabolismofthe endocannabinoidsandtheirbiologicaltargetsarebeginningtobeunravelled,but the degree of complexity involved is enormous. This is particularly true for endocannabinoidsignallinginthecentralnervoussystem,whichisthesubjectof thisvolume. Inthebook,avarietyofauthors,whoareallveryactiveresearchersinthe?eld, providecurrentaccountsoftherolesoftheendocannabinoidsysteminnormalbrain physiologyinrelationtotheneurobiologyofessentialbehaviorsandinanumberof centraldiseasestates. The?rstpartprovidesabackgroundand"toolbox",detailingwhatisknown abouttheendocannabinoidsthemselvesandtheirtargetreceptorsandhowthey in?uencesynapticactivity. Itgoesontodescribethegeneticandpharmacological methodsavailableforinvestigatingthesystem. The second part describes endocannabinoid roles in key systems controlling appetite,pain,memoryandlearning,stressresponsesandreproduction. The?nalgroupofchaptersreviewsthecurrentstateofknowledgesurrounding thefunctionoftheendocannabinoidsystemindepression,drugaddiction,schi- phrenia,feedingdisordersandTourette'ssyndrome. Giventheenormousamountofinformationavailableandtherateofprogressin research,itisimpossibleforthevolumetobetotallycomprehensive,butwetrust thatitwillprovideanexcellentbackgroundtoresearcherswantingtoexpandtheir areaofinterestandtonewcomerstothe?eld. Nottingham,UnitedKingdom DavidKendall StephenAlexander v Contents PartI Biochemistry,Pharmacology,GeneticsandChemistry 1 TheLifeCycleoftheEndocannabinoids:Formation andInactivation...3 StephenP. H. AlexanderandDavidA. Kendall 2 EndocannabinoidReceptorPharmacology ...37 KenMackieandBettyYao 3 EndocannabinoidReceptors:CNSLocalizationoftheCB 1 CannabinoidReceptor...65 Istva'nKatona 4 PharmacologicalToolsinEndocannabinoidNeurobiology...87 MarcoMorandAlessioLodola 5 GeneticModelsoftheEndocannabinoidSystem ...111 KrisztinaMonoryandBeatLutz 6 EndocannabinoidSignalinginNeuralPlasticity ...141 BradleyE. Alger 7 LessonsfromNonmammalianSpecies ...173 KenSoderstrom PartII PhysiologyandPathophysiology 8 RolesoftheEndocannabinoidSysteminLearning andMemory ...201 GiovanniMarsicanoandPaulineLafenetre vii viii Contents 9 EndocannabinoidsandtheNon-HomeostaticControl ofAppetite ...231 TimC. Kirkham 10 Cannabinoid/EndocannabinoidSignalingImpactonEarly PregnancyEvents...255 XiaofeiSunandSudhansuK. Dey 11 TargetingtheCannabinoidSystemtoProduceAnalgesia ...275 DeviRaniSagar,MaulikJhaveri,andVictoriaChapman 12 IntegrationofEndocannabinoidSignalingintotheNeural NetworkRegulatingStress-InducedActivationofthe Hypothalamic-Pituitary-AdrenalAxis ...289 BorisB. GorzalkaandMatthewN. Hill PartIII Pathology 13 DrugAddiction ...309 ZuzanaJustinova,LeighV. Panlilio,andStevenR. Goldberg 14 RoleofEndocannabinoidSignalinginAnxietyandDepression...347 SachinPatelandCeciliaJ. Hillard 15 FeedingDisordersandObesity...373 CristinaCervino,ValentinaVicennati,RenatoPasquali, andUbertoPagotto 16 Schizophrenia...387 F. Markus 17 Tourette'sSyndrome...397 KirstenR. Mu..ller-Vahl Index ...411 Contributors StephenP. H. Alexander SchoolofBiomedicalSciencesandInstituteofNeuroscience,UniversityofN- tingham Medical School, Queens Medical Centre, Nottingham NG7 2UH, UK; steve. alexander@nottingham. ac. uk BradleyE. Alger Departments of Physiology and Psychiatry, University of Maryland School of Medicine, 655 W. Baltimore St. /BRB 5-025, Baltimore, MD 21201, USA; balger@umaryland. edu CristinaCervino Endocrinology Unit and Center of Applied Biomedical Research (C. R. B. A. ), DepartmentofInternalMedicineandGastroenterology,S. Orsola-MalpighiHos- tal,AlmaMaterStudiorumUniversityofBologna,40138Bologna,Italy VictoriaChapman SchoolofBiomedicalSciences,UniversityofNottingham,NottinghamNG72UH, UK;victoria. chapman@nottingham. ac. uk SudhansuK. Dey Departments of Pharmacology, Pediatrics and Cell & Developmental Biology, Division of Reproductive and Developmental Biology, Vanderbilt University MedicalCenter,Nashville,TN37232,USA;sk. dey@vanderbilt. edu StevenR.

This thoroughly updated edition covers all clinical aspects of neuroinflammation. The latest developments in pathogenesis and advances in treatment are provided, along with an understanding of the immune system's role and interactions between the activated immune cells, cerebral endothelial cells, and other main components of the immune cascade. Cutting-edge and authoritative, this volume offers practitioners a valuable resource for research and clinical practice.

Are your exams coming up? Are you drowning in textbooks and lecture notes and wondering where to begin? Take the "FASTtrack" route to successful study for your examinations. "FASTtrack" provides the ultimate lecture notes and is a must-have for all pharmacy students wanting to study and test themselves for forthcoming exams. "FASTtrack: Pharmacology" provides a brief account of drug action, as either a study or revision aid. In doing this, the authors have generally taken a therapeutic area and considered the major classes of drugs, their actions and, to a limited degree, their uses. There are many excellent brief guides to pharmacology and so their second aim is to present a study guide which deals with molecular pharmacology at a more advanced level, so that the book is also useful for advanced pharmacology studied in the later years of pharmacy and science degrees. This study guide should therefore be useful at each level of undergraduate study.New in this edition: each chapter completely updated to take account of recent changes, and include future drugs; multiple choice tests; new chapters on immunopharmacology, oral contraceptives and local anaesthetics; and, greater use of summary tables.