Abstract:
:Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.
journal_name
Naturejournal_title
Natureauthors
Conrad KL,Tseng KY,Uejima JL,Reimers JM,Heng LJ,Shaham Y,Marinelli M,Wolf MEdoi
10.1038/nature06995subject
Has Abstractpub_date
2008-07-03 00:00:00pages
118-21issue
7200eissn
0028-0836issn
1476-4687pii
nature06995journal_volume
454pub_type
杂志文章相关文献
NATURE文献大全abstract::Osteoclasts are multinucleated giant cells that resorb bone, ensuring development and continuous remodelling of the skeleton and the bone marrow haematopoietic niche. Defective osteoclast activity leads to osteopetrosis and bone marrow failure1-9, whereas excess activity can contribute to bone loss and osteoporosis10....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1105-7
更新日期:2019-04-01 00:00:00
abstract::The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25170
更新日期:2018-01-18 00:00:00
abstract::The homeobox is a 183-base-pair DNA sequence originally found in Drosophila segmentation and homeotic genes. In Drosophila, homeotic genes are clustered in the Antennapedia and Bithorax complexes, collectively called the homeotic gene complex (HOM-C). In the mouse genome, about 40 homeobox genes (Hox) are clustered in...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/365069a0
更新日期:1993-09-02 00:00:00
abstract::Novel capsomeric complexes, pentamers and hexamers were detected as chemical entities in phage Q beta. Both were composed of identical protein subunits and stabilized by intermolecular disulphide bonds. Their numbers per particle were about 12 for pentamers and about 20 for hexamers--consistent with theoretical expect...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/298819a0
更新日期:1982-08-26 00:00:00
abstract::Repetitive activation of excitatory synapses in the central nervous system results in a long-lasting increase in synaptic transmission called long-term potentiation (LTP). It is generally believed that this synaptic plasticity may underlie certain forms of learning and memory. LTP at most synapses involves the activat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/41574
更新日期:1997-08-07 00:00:00
abstract::A fundamental challenge to our understanding of biodiversity is to explain why some groups of species undergo adaptive radiations, diversifying extensively into many and varied species, whereas others do not. Both extrinsic environmental factors (for example, resource availability, climate) and intrinsic lineage-speci...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11144
更新日期:2012-07-19 00:00:00
abstract::Oxygenic photosynthesis in plants, algae and cyanobacteria is initiated at photosystem II, a homodimeric multisubunit protein-cofactor complex embedded in the thylakoid membrane. Photosystem II captures sunlight and powers the unique photo-induced oxidation of water to atmospheric oxygen. Crystallographic investigatio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04224
更新日期:2005-12-15 00:00:00
abstract::Although it has been proposed that the activation of T lymphocytes is mediated by an early rise in cytosolic calcium concentration, it has not been possible to mimic antigen- or mitogen-induced mouse lymphocyte activation by calcium ionophores that bypass receptor-mediated processes. There is now evidence from other s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/313318a0
更新日期:1985-01-24 00:00:00
abstract::The motility of the gastrointestinal tract consists of local, non-propulsive mixing (pendular or segmental) and propulsive (peristaltic) movements. It is generally considered that mixing movements are produced by intrinsic pacemakers which generate rhythmic contractions, and peristalsis by intrinsic excitatory and inh...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/19973
更新日期:1999-05-06 00:00:00
abstract::Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis1,2. Recent studies have demonstrated that Treg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4+ effecto...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0846-z
更新日期:2019-01-01 00:00:00
abstract::Oxygen and silicon isotope compositions of cherts and studies of protein evolution have been interpreted to reflect ocean temperatures of 55-85 degrees C during the early Palaeoarchaean era ( approximately 3.5 billion years ago). A recent study combining oxygen and hydrogen isotope compositions of cherts, however, mak...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature08952
更新日期:2010-04-15 00:00:00
abstract::Concern about the levels of lead in blood is widespread. There is uncertainty, however, about the relative importance of the various environmental sources. Lead in petrol is widely assumed to be one of the most important sources and air and dust have been identified as the main routes to man. Water is regarded as an i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/310138a0
更新日期:1984-07-12 00:00:00
abstract::Germinal centres are specialized structures wherein B lymphocytes undergo clonal expansion, class switch recombination, antibody gene diversification and affinity maturation. Three to four antigen-specific B cells colonize a follicle to establish a germinal centre and become rapidly dividing germinal-centre centroblas...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05573
更新日期:2007-03-01 00:00:00
abstract::The assembly of ribosomes in bacterial cells is a complex process that remains poorly characterized. The in vitro assembly of active ribosomal subunits from purified RNA and protein components indicates that all of the information for proper assembly resides in the primary sequences of these macromolecules. On the oth...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/336496a0
更新日期:1988-12-01 00:00:00
abstract::It is widely accepted that obesity and associated metabolic diseases, including type 2 diabetes, are intimately linked to diet. However, the gut microbiota has also become a focus for research at the intersection of diet and metabolic health. Mechanisms that link the gut microbiota with obesity are coming to light thr...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature18846
更新日期:2016-07-07 00:00:00
abstract::Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/318064a0
更新日期:1985-11-07 00:00:00
abstract::Chromosome conformation capture methods have identified subchromosomal structures of higher-order chromatin interactions called topologically associated domains (TADs) that are separated from each other by boundary regions. By subdividing the genome into discrete regulatory units, TADs restrict the contacts that enhan...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature19800
更新日期:2016-10-13 00:00:00
abstract::The genes for the T-cell receptor, like the immunoglobulin genes, are rearranged as DNA. The mechanism of this rearrangement is not clear; unequal crossover between chromosomes and the looping-out and excision of the excess DNA have both been suggested. We isolated small polydisperse circular (spc) DNAs from mouse thy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/327242a0
更新日期:1987-05-21 00:00:00
abstract::The effect of ions on the light-sensitive current of retinal rods was studied by sucking the inner segment into a tightly fitting capillary with the outer segment projecting into a flowing solution. This new method showed that the light-sensitive pathway, in which Na+ is the normal carrier of current, has an ionic sel...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/292502a0
更新日期:1981-08-06 00:00:00
abstract::Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human c...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07385
更新日期:2008-10-23 00:00:00
abstract::A combination of biochemistry in animal cell-free systems and genetics in yeast is revealing the molecular machinery of the secretory pathway of eukaryotes. Transporting vesicles have a simple coat structure and employ a general mechanism for fusion that is conserved in evolution. ...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/355409a0
更新日期:1992-01-30 00:00:00
abstract::A popular metaphor for the representation of numbers in the brain is the 'mental number line', in which numbers are represented in a continuous, quantity-based analogical format. Here we show that patients with hemispatial neglect misplace the midpoint of a numerical interval when asked to bisect it (for example, stat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/417138a
更新日期:2002-05-09 00:00:00
abstract::Regulatory T (T(reg)) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease, and for regulating homeostatic lymphocyte expansion. However, they also sup...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06306
更新日期:2007-11-22 00:00:00
abstract::Phosphatidylinositol 4,5-bisphosphate (PIP2), which comprises only about 1% of the phospholipids in the cytoplasmic leaflet of the plasma membrane, is the source of three second messengers, activates many ion channels and enzymes, is involved in both endocytosis and exocytosis, anchors proteins to the membrane through...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature04398
更新日期:2005-12-01 00:00:00
abstract::The 18-base-pair sequence element AGGTCGACCAGTACTCCG (the Sal box) signals termination of mouse ribosomal gene transcription. This sequence is recognized by a sequence-specific DNA-binding protein, TTF I, which mediates the termination of transcription by RNA polymerase I (pol I). Subsequently, the ends of the primary...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/344559a0
更新日期:1990-04-05 00:00:00
abstract::After an earthquake, numerous smaller shocks are triggered over distances comparable to the dimensions of the mainshock fault rupture, although they are rare at larger distances. Here we analyse the scaling of dynamic deformations (the stresses and strains associated with seismic waves) with distance from, and magnitu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/437830a
更新日期:2005-10-06 00:00:00
abstract::This corrects the article DOI: 10.1038/nature19356. ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/nature24643
更新日期:2017-11-16 00:00:00
abstract::Direct dating of ductile shear zones and calculation of uplift/exhumation rates can be done using various radiometric dating techniques. But radiometric dating of shallow crustal faulting, which occurs in the crust's brittle regime, has remained difficult because the low temperatures typical of shallow crusted faults ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35084053
更新日期:2001-07-12 00:00:00
abstract::Ants travelling to and fro between their nest and a foraging area may follow stereotyped foodward and homeward routes that are guided by different visual and directional memory sequences. Honeybees are known to fly a feeder-to-hive or hive-to-feeder vector according to whether or not they have recently fed--their feed...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/438302a
更新日期:2005-11-17 00:00:00
abstract::Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1471-1
更新日期:2019-08-01 00:00:00