Abstract：
:Drugs of abuse are very powerful reinforcers, and even in conditions of limited access (where the organism is not dependent) these drugs will motivate high rates of operant responding. This presumed hedonic property and the drugs' neuropharmacological specificity provide a means of studying the neuropharmacology and neuroanatomy of brain reward. Three major brain systems appear to be involved in drug reward--dopamine, opioid and GABA. Evidence suggests a midbrain-forebrain-extrapyramidal circuit with its focus in the nucleus accumbens. Data implicating dopamine and opioid systems in indirect sympathomimetic and opiate reward include critical elements in both the nucleus accumbens and ventral tegmental areas. Ethanol reward appears to depend on an interaction with the GABAA receptor complex but may also involve common elements such as dopamine and opioid peptides in this midbrain-forebrain-extrapyramidal circuit. These results suggest that brain reward systems have a multidetermined neuropharmacological basis that may involve some common neuroanatomical elements.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Koob GFdoi
10.1016/0165-6147(92)90060-jsubject
Has Abstractpub_date
1992-05-01 00:00:00pages
177-84issue
5eissn
0165-6147issn
1873-3735pii
0165-6147(92)90060-Jjournal_volume
13pub_type
杂志文章,评审abstract：:Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate micr...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.04.005
更新日期：2019-06-01 00:00:00
abstract：:Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease that is caused by cigarette smoke. The main characteristic of COPD is the continued inflammation caused by the sustained influx of macrophages and neutrophils into the lung. Recent studies have shed light on how these cells are attracted ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2006.09.003
更新日期：2006-11-01 00:00:00
abstract：:Gene therapy is a new field of medical research that has great potential to influence the course of treatment of human disease. The lung has been a particularly attractive target organ for gene therapy due to its accessibility and the identification of genetic deficits for a number of lung diseases. Several clinical t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01350-4
更新日期：1999-06-01 00:00:00
abstract：:Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2019.04.015
更新日期：2019-07-01 00:00:00
abstract：:Pharmacological studies as well as molecular cloning of 5-HT receptors have revealed a multiplicity of receptor subtypes, not only in mammals but, as discussed in this review by René Hen, also in molluscs and arthropods. Most of these receptors belong to the G protein-coupled receptor family, and their mechanism of ac...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(92)90054-a
更新日期：1992-04-01 00:00:00
abstract：:The phospholipase A2 enzymes are important components of the cellular machinery that responds to inflammatory stimuli and maintains cell homeostasis by membrane remodelling. Their role as the rate-limiting step in the production of pro-inflammatory lipid mediators makes these enzymes an important therapeutic target fo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(93)90071-q
更新日期：1993-03-01 00:00:00
abstract：:The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01675-8
更新日期：2001-04-01 00:00:00
abstract：:Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.09.002
更新日期：2020-11-01 00:00:00
abstract：:The ability to target specific cell types to achieve optimal distribution of therapeutic entities into diseased tissues, while limiting possible adverse off-target effects, has long been a goal of many research groups and pharmaceutical organizations. This review focuses on peptidic tissue-specific biomarkers that all...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.02.002
更新日期：2012-04-01 00:00:00
abstract：:HIV-1 integrase (IN) executes the insertion of proviral DNA into the host cell genome, an essential step in the retroviral life cycle. This is a multi-step process that starts in the cytosol and culminates in the nucleus of the infected cell. It is becoming increasingly clear that IN interacts with a wide range of dif...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.09.005
更新日期：2007-10-01 00:00:00
abstract：:Folates are essential for key biosynthetic processes in mammalian cells and play a crucial role in the maintenance of central nervous system homeostasis. Mammals lack the metabolic capacity for folate biosynthesis; hence, folate requirements are largely met through dietary sources. To date, three major folate transpor...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.02.004
更新日期：2020-05-01 00:00:00
abstract：:Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01596-0
更新日期：2001-01-01 00:00:00
abstract：:The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01090-0
更新日期：1997-08-01 00:00:00
abstract：:N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diver...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2011.08.003
更新日期：2011-12-01 00:00:00
abstract：:Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of AGXT2 was largely overlooked for three decades because AGXT2 is less active in glyoxylate metabolism than AGXT1, the enzyme that is deficient in primary h...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.09.005
更新日期：2014-11-01 00:00:00
abstract：:The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01201-2
更新日期：1998-05-01 00:00:00
abstract：:Due to its negative chronotropic and inotropic effects, adenosine has to date been considered as a cardiodepressant agent. However, adenosine increases ventricular automaticity. This review by Jesus Hernández and Alexandre Ribeiro discusses the experimental and clinical evidence for the excitatory effects of adenosine...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(96)81589-6
更新日期：1996-04-01 00:00:00
abstract：:Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
journal_title：Trends in pharmacological sciences
pub_type： 评论,信件
doi：10.1016/j.tips.2016.06.001
更新日期：2016-08-01 00:00:00
abstract：:The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-rela...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90637-8
更新日期：1991-12-01 00:00:00
abstract：:The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/l...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.06.008
更新日期：2015-10-01 00:00:00
abstract：:The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.02.003
更新日期：2017-05-01 00:00:00
abstract：:Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2014.07.001
更新日期：2014-09-01 00:00:00
abstract：:In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.02.008
更新日期：2015-05-01 00:00:00
abstract：:Much regarding the engagement of the G(12) family of heterotrimeric G proteins (G(12) and G(13)) by agonist-activated receptors remains unclear. For example, the identity of receptors that couple unequivocally to G(12) and G(13) and how signals are allocated among these and other G proteins remain open questions. Part...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.01.007
更新日期：2005-03-01 00:00:00
abstract：:The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in a...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.07.003
更新日期：2006-09-01 00:00:00
abstract：:A diet low in carbohydrates helps to reduce the amount of ingested calories and to maintain a healthy weight. With this in mind, food and beverage companies have reformulated a large number of their products, replacing sugar or high fructose corn syrup with several different types of zero-calorie sweeteners to decreas...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2011.06.007
更新日期：2011-11-01 00:00:00
abstract：:Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.09.004
更新日期：2013-11-01 00:00:00
abstract：:The myeloid-derived suppressor cell (MDSC) is the 'queen bee' of the tumor microenvironment. MDSCs protect the cancer from the patient's immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer ther...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.10.008
更新日期：2019-01-01 00:00:00
abstract：:Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties. Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studie...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.05.006
更新日期：2010-08-01 00:00:00
abstract：:Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1989-12-01 00:00:00
