Generalized cue reactivity in dopamine neurons after opioids DOI Creative Commons

Collin M. Lehmann,

Nora E. Miller,

Varun S. Nair

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 2, 2024

Abstract Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues a major driver of relapse. The leading hypothesis that dopamine release by addictive drugs represents persistently positive reward prediction error causes runaway enhancement responses cues, their pathological overvaluation compared non-drug alternatives. However, this has not been directly tested. Here we developed Pavlovian operant procedures measure firing responses, within same neurons, versus natural which found be similarly enhanced predicting rewards in drug-naïve controls. This was associated with increased cue, suggesting still critical cue reactivity, albeit as previously hypothesized. These results challenge prevailing warranting new models dopaminergic function addiction, provide insights into neurobiology potential implications for relapse prevention.

Language: Английский

Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need DOI
Bowen Tan, Caleb J. Browne, Tobias Nöbauer

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates signal transduction NAc while enabling suppress consumption. Mapping NAc-projecting regions activated revealed input-specific effects on These findings characterize dynamic, circuit basis common pathway, wherein interfere with fulfillment innate needs.

Language: Английский

Citations

30

A cellular and molecular basis of leptin resistance DOI Creative Commons
Bowen Tan, Kristina Hedbacker,

Leah Kelly

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: 37(3), P. 723 - 741.e6

Published: March 1, 2025

Similar to most humans with obesity, diet-induced obese (DIO) mice have high leptin levels and fail respond the exogenous hormone, suggesting that their obesity is caused by resistance, pathogenesis of which unknown. We found treatment reduced plasma leucine methionine, mTOR-activating ligands, leading us hypothesize chronic mTOR activation might reduce signaling. Rapamycin, an inhibitor, fat mass increased sensitivity in DIO but not defects Rapamycin restored leptin's actions on POMC neurons failed weight melanocortin whereas POMC-specific mutations activators decreased gain mice. Thus, activity necessary sufficient for development resistance mice, establishing a key pathogenic mechanism obesity.

Language: Английский

Citations

3

Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression DOI Creative Commons
Farid Aboharb, Pasha A. Davoudian,

Ling-Xiao Shao

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

Language: Английский

Citations

2

Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety DOI
Zhenggang Zhu, Rong Gong,

Vicente Martínez Rodríguez

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6741)

Published: March 27, 2025

Hedonic eating is defined as food consumption driven by palatability without physiological need. However, neural control of palatable intake poorly understood. We discovered that hedonic controlled a pathway from the peri–locus ceruleus to ventral tegmental area (VTA). Using photometry-calibrated optogenetics, we found VTA dopamine (VTA DA ) neurons encode bidirectionally regulate consumption. neuron responsiveness was suppressed during semaglutide, glucagon-like peptide receptor 1 (GLP-1R) agonist used an antiobesity drug. Mice recovered appetite and activity repeated semaglutide treatment, which reversed consumption-triggered inhibition. Thus, activates neurons, sustain further consumption, mechanism opposes reduction semaglutide.

Language: Английский

Citations

2

Opioid use and abuse in adolescents and young adults; dealing with science, laws and ethics: Charming the COBRAS DOI

Donald E. Greydanus,

Ahsan Nazeer, Dilip R. Patel

et al.

Disease-a-Month, Journal Year: 2025, Volume and Issue: unknown, P. 101853 - 101853

Published: Jan. 1, 2025

Language: Английский

Citations

1

Reelin marks cocaine-activated striatal neurons, promotes neuronal excitability, and regulates cocaine reward DOI
Kasey L. Brida, Emily T. Jorgensen, Robert A. Phillips

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 26, 2025

Drugs of abuse activate defined neuronal populations in reward structures such as the nucleus accumbens (NAc), which promote enduring synaptic, circuit, and behavioral consequences drug exposure. While molecular cellular effects arising from experience with drugs like cocaine are increasingly well understood, mechanisms that dictate NAc recruitment remain unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling targeted situ detection to identify Reln (encoding secreted glycoprotein, Reelin) a marker cocaine-activated within rat NAc. A CRISPR interference approach enabling selective knockdown adult altered expression calcium signaling genes, promoted trajectory consistent loss sensitivity, decreased MSN excitability. Behaviorally, prevented locomotor sensitization, abolished place preference memory, self-administration behavior. These results Reelin critical mechanistic link between activation cocaine-induced adaptations.

Language: Английский

Citations

1

Generalized cue reactivity in rat dopamine neurons after opioids DOI Creative Commons

Collin M. Lehmann,

Nora E. Miller,

Varun S. Nair

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

Citations

1

Neurotransmitters crosstalk and regulation in the reward circuit of subjects with behavioral addiction DOI Creative Commons
Zhenlei Peng, Qiyu Jia,

Junxiong Mao

et al.

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Behavioral addictive disorders (BADs) have become a significant societal challenge over time. The central feature of BADs is the loss control engaging in and continuing behaviors, even when facing negative consequences. neurobiological underpinnings primarily involve impairments reward circuitry, encompassing ventral tegmental area, nucleus accumbens striatum, prefrontal cortex. These brain regions form networks that communicate through neurotransmitter signaling, leading to changes individuals with behavioral addictions. While dopamine has long been associated process, recent research highlights role other key neurotransmitters like serotonin, glutamate, endorphins BADs' development. interact within creating potential targets for therapeutic intervention. This improved understanding systems provides foundation developing targeted treatments helps clinicians select personalized approaches.

Language: Английский

Citations

1

Neurobiological mechanisms of nicotine's effects on feeding and body weight DOI
Y. Li, Jian Mao,

Guobi Chai

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: 169, P. 106021 - 106021

Published: Jan. 16, 2025

Language: Английский

Citations

1

Cocaine and morphine induce shared and divergent transcriptional regulation in nucleus accumbens D1 and D2 medium spiny neurons DOI
Caleb J. Browne, Philipp Mews,

Molly Estill

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Language: Английский

Citations

1