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This chapter presents a reliable, detailed method for performing double-label in situ hybridization (ISH) that has been validated for use in studies identifying the co-localization of cannabinoid CB1 receptor mRNA with other distinct species of mRNAs. This method permits simultan ...

During the last decade, numerous cannabinergic ligands with high affinity and selectivity profiles for cannabinoid receptors (CB1 and CB2) emerged from rigorously pursued structure-activity relationship studies. This chapter focuses on the synthetic aspects of key cannabi ...

The use of electrophysiological recordings in brain slices is now routinely used to assess the actions of cannabinoid ligands within various central nervous system nuclei. In this chapter we describe common protocols involving both intracellular and extracellular recording te ...

One of the major goals for the use of digital image analysis systems in neuroanatomy is to visualize structures, cells, or other tissue components in order to compare various populations. In addition, digital image analysis allows semi-quantification of cell labeling because it is capable ...

Radioligand-binding assays can be used to obtain information about the binding characteristics of a ligand to its receptor or the general location of binding sites within a tissue or even provide evidence for the existence of a specific receptor. In the case of the cannabinoid receptor system, ...

Anandamide (AEA) is the most studied member of a new class of lipid mediators, collectively called endocannabinoids. The biological activity of AEA at cannabinoid and noncannabinoid receptors depends on its life span in the extracellular space, which is regulated by a rapid cellular upta ...

There is increasing pressure from patients, health care providers, regulatory authorities, and pharmaceutical companies and their shareholders to bring safer drugs to the market. Despite highly regulated preclinical screening and clinical monitoring, drugs do still make it on ...

The release of millions of polymorphisms by recently completed, large- scale sequencing and genotyping efforts has provided us with unprecedented resources for carrying out genetic association analyses of drug response and disease predisposition. This chapter provides a guide ...

Pharmacogenetics research focuses on the identification of inherited DNA sequence variations that influence an individual's response to therapeutic agents. Discovering such variations is nontrivial and may require enormous and potentially unrealistic sample sizes for a ...

Pharmacogenomics is an extension of pharmacogenetics, a science described here in terms of five stages of development: 1) some clinical observations predicted genetic alterations of drug response; 2) additional case discoveries led to the term “pharmacogenetics,” a concept broad ...

Adverse drug reactions (ADRs) are a major clinical problem. A rapidly growing body of evidence suggests that genetic factors, at least in part, determine individual susceptibility to ADRs. A large number of pharmacogenetic studies have identified a number of polymorphisms as predicto ...

The analysis of gene differential expression is complicated by the potentially subtle differences associated with alterations in a single allele as well as by variations between individuals that arise from environmental or physiological factors. To circumvent these analytic p ...

Human variation is largely caused by deoxyribonucleic acid polymorphism and difference in gene expression. Common disease/common variant hypotheses suggest that quantitative differences among different alleles may be the basis for complex diseases. Quantitative diffe ...

The characterization of protein-deoxyribonucleic acid (DNA) interactions occurring at an allele-specific level is important to resolving the functional consequences of genetic variation in non-coding DNA for gene expression and regulation. The approach of haplotype-spe ...

Major strengths of mass spectrometry analysis include the accuracy of the detection principle and the automatic data storage, making it a premier choice for high-throughput single-nucleotide polymorphism genotyping. We explain the assay principle in detail and give step-by-step ...

To undertake partial, or complete, genome screens by association-based methodology for quantitative trait loci, multiple individuals have to be screened for large numbers of genetic markers. Consequently, much recent interest has focused on methods enabling accurate allele qua ...

The successful application of capillary electrophoresis technology to the genotyping of various types of polymorphisms has been well documented. The flexibility and automation of the Applied Biosystems 3100 Genetic Analyzer make it an excellent capillary electrophoresis p ...

The 5′ fluorogenic (TaqMan) assay has been successfully used in screening for singlenucleotide polymorphisms; the very few steps required and the ability to automate each step allow for high-throughput screening. Insertion/deletion polymorphisms are an important class of marke ...

The variety of genotyping methods currently available and the evolution of their capabilities have facilitated an expansion of the field of pharmacogenomics. Traditionally, limited genotyping capabilities have restricted the generation and application of genotyping data ...

The data generated from the Human Genome Project has led to an explosion of technology for low-, medium-, and high-throughput genotyping methods. Pyrosequencing is a genotyping assay based on sequencing by synthesis. Short runs of sequence around each polymorphism are generated, allowi ...