Abstract：
:Poorly regulated reward seeking is a central feature of substance use disorder. Recent research shows that rewarding drug-related experiences induce synchronous activation of a discrete number of neurons in the nucleus accumbens that are causally linked to reward-related contexts. Here we comprehensively characterize the specific ensemble of neurons built through experience that are linked to seeking behavior. We additionally address the question of whether or not addictive drugs usurp the neuronal networks recruited by natural rewards by evaluating cocaine- and sucrose-associated ensembles within the same mouse. We used FosCreERT2/+/Ai14 transgenic mice to tag cells activated by and potentially encoding cocaine and sucrose seeking. We tagged ~1% of neurons in the core subregion of the accumbens (NAcore) activated during cue-induced seeking for cocaine or sucrose. The majority of tagged cells in the seeking ensembles were D1-MSNs, and specifically activated during seeking, not during extinction or when mice remained in the home cage. To compare different reward-specific ensembles within the same mouse, we used a dual cocaine and sucrose self-administration protocol allowing reward-specific seeking. Using this model, we found ~70% distinction between the cells constituting the cocaine- compared to the sucrose-seeking ensemble. Establishing that cocaine recruits an ensemble of NAcore neurons largely distinct from neurons recruited into an ensemble coding for sucrose seeking suggest a finely tuned specificity of ensembles. The findings allow further exploration of the mechanisms that transform reward-based positive reinforcement into maladaptive drug seeking.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Bobadilla AC,Dereschewitz E,Vaccaro L,Heinsbroek JA,Scofield MD,Kalivas PWdoi
10.1038/s41380-020-00888-zsubject
Has Abstractpub_date
2020-12-01 00:00:00pages
3150-3163issue
12eissn
1359-4184issn
1476-5578pii
10.1038/s41380-020-00888-zjournal_volume
25pub_type
杂志文章abstract：:Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoh...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000365
更新日期：1998-03-01 00:00:00
abstract：:The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.7
更新日期：2009-06-01 00:00:00
abstract：:The human 16p11.2 gene locus is a hot spot for copy number variations, which predispose carriers to a range of neuropsychiatric phenotypes. Microduplications of 16p11.2 are associated with autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia (SZ). Despite the debilitating nature of 16p11.2 d...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0693-9
更新日期：2020-02-25 00:00:00
abstract：:Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is m...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0387-3
更新日期：2020-11-01 00:00:00
abstract：:Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellula...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2014.111
更新日期：2014-11-01 00:00:00
abstract：:Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hypera...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2014.90
更新日期：2015-06-01 00:00:00
abstract：:The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associa...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001809
更新日期：2006-04-01 00:00:00
abstract：:Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to de...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.18
更新日期：2009-12-01 00:00:00
abstract：:The Raf kinases Raf-1 and B-Raf are upstream activators of the extracellular signal-regulated kinase (ERK)-signaling pathway and therefore participates in many physiological functions in brain, including neuronal survival and synaptic plasticity. Previously, we observed that activation of ERK-1/2, the downstream compo...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001744
更新日期：2006-01-01 00:00:00
abstract：:We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,评审
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更新日期：2009-04-01 00:00:00
abstract：:Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognit...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.182
更新日期：2017-02-01 00:00:00
abstract：:The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001062
更新日期：2002-01-01 00:00:00
abstract：:Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls. Since this may reflect altered reuptake by the norepinephrine transporter (NET), we hypothesised that the NET gene was involved in the genetic component of AN. PCR-amplification of an AAGG repeat island (AAGG1...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001080
更新日期：2002-01-01 00:00:00
abstract：:Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysi...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,多中心研究
doi：10.1038/mp.2011.125
更新日期：2012-12-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.187
更新日期：2018-02-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001067
更新日期：2002-01-01 00:00:00
abstract：:Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.2
更新日期：2013-01-01 00:00:00
abstract：:Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood....
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.80
更新日期：2018-05-01 00:00:00
abstract：:We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001463
更新日期：2004-04-01 00:00:00
abstract：:DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0605-z
更新日期：2019-12-06 00:00:00
abstract：:Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neon...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.130
更新日期：2016-07-01 00:00:00
abstract：:Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations hav...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0355-y
更新日期：2020-04-01 00:00:00
abstract：:Human cytomegalovirus (HCMV) infection is associated with neuropathology in patients with impaired immunity and/or inflammatory diseases. However, the association between gray matter volume (GMV) and HCMV has never been examined in major depressive disorder (MDD) despite the presence of inflammation and impaired viral...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-00932-y
更新日期：2020-11-22 00:00:00
abstract：:Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2011.148
更新日期：2013-02-01 00:00:00
abstract：:We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001224
更新日期：2003-01-01 00:00:00
abstract：:Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck is the difficulty in modeling depressive episodes in animals. Here, we show that a transgenic mouse with chronic forebrain expression of a dominant negative mutant of Polg1, a mitochondrial DNA (mtDNA...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.156
更新日期：2016-01-01 00:00:00
abstract：:Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encod...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/s41380-018-0036-2
更新日期：2019-01-01 00:00:00
abstract：:Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizo...
journal_title：Molecular psychiatry
pub_type： 杂志文章,随机对照试验
doi：10.1038/mp.2017.41
更新日期：2018-02-01 00:00:00
abstract：:Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.82
更新日期：2017-02-01 00:00:00
abstract：:Attention-deficit hyperactivity disorder (ADHD) is typically characterized as a disorder of inattention and hyperactivity/impulsivity but there is increasing evidence of deficits in motivation. Using positron emission tomography (PET), we showed decreased function in the brain dopamine reward pathway in adults with AD...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2010.97
更新日期：2011-11-01 00:00:00
