Sexually dimorphic development of the mesolimbic dopamine system is associated with nuanced sensitivity to adolescent alcohol use DOI Creative Commons

Ari M. Asarch,

Lauren C. Kruse,

Abigail G. Schindler

и другие.

Frontiers in Behavioral Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Фев. 22, 2023

Alcohol use remains a major public health concern and is especially prevalent during adolescence. Adolescent alcohol has been linked to several behavioral abnormalities in later life, including increased risk taking impulsivity. Accordingly, when modeled animals, male rats that had moderate consumption adolescence exhibit multiple effects adulthood, taking, altered incentive learning, greater release of dopamine the mesolimbic pathway. It proposed arrests neural development, "locking in" adolescent physiological, consequent behavioral, phenotypes. Here we examined feasibility elevated levels following exposure are "locked phenotype by testing across development. We found rats, peaks late adolescence, returning lower consistent with notion high adolescence-alcohol-exposed adults were due arrested Surprisingly, females was stable tested developmental window. This result raised quandary would not differ from normal development and, therefore, may contribute pathological behavior. However, aforementioned findings related risk-based decision-making have only performed subjects. When undergone use, neither attitude probabilistic nor altered. These suggest different profiles system sexes dimorphic susceptibility alcohol-induced cognitive motivational anomalies exposure.

Язык: Английский

An opponent striatal circuit for distributional reinforcement learning DOI Creative Commons
Adam S. Lowet, Zheng Qiao, Melissa Meng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 3, 2024

Abstract Machine learning research has achieved large performance gains on a wide range of tasks by expanding the target from mean rewards to entire probability distributions — an approach known as distributional reinforcement (RL) 1 . The mesolimbic dopamine system is thought underlie RL in mammalian brain updating representation value striatum 2,3 , but little about whether, where, and how neurons this circuit encode information higher-order moments reward 4 To fill gap, we used high-density probes (Neuropixels) acutely record striatal activity well-trained, water-restricted mice performing classical conditioning task which mean, variance, stimulus identity were independently manipulated. In contrast traditional accounts, found robust evidence for abstract encoding variance striatum. Remarkably, chronic ablation inputs disorganized these representations without interfering with coding. Two-photon calcium imaging optogenetics revealed that two major classes medium spiny D1 D2 MSNs contributed code preferentially right left tails distribution, respectively. We synthesize findings into new model harnesses opponency between 5–15 reap computational benefits RL.

Язык: Английский

Процитировано

6
A Roadmap for Transformative Translational Research on Gambling Disorder in the UK Funded by A New Levy on The Gambling Industry DOI Creative Commons
Tristan Hynes, Henrietta Bowden‐Jones, Samuel R. Chamberlain

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106071 - 106071

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Adverse events associated with four atypical antipsychotics used as augmentation treatment for major depressive disorder: A pharmacovigilance study based on the FAERS database DOI
F. Z. Qi, Longlong Tian,

H L Diao

и другие.

Journal of Affective Disorders, Год журнала: 2025, Номер unknown, С. 119435 - 119435

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Noradrenergic regulation of cue-guided decision making and impulsivity is doubly dissociable across frontal brain regions DOI Creative Commons
Chloe S. Chernoff, Tristan Hynes,

Jackson D. Schumacher

и другие.

Psychopharmacology, Год журнала: 2023, Номер 241(4), С. 767 - 783

Опубликована: Ноя. 25, 2023

Abstract Rationale Win-paired stimuli can promote risk taking in experimental gambling paradigms both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, guanfacine, selective α2A adrenergic receptor agonist, reduced on the cued rat task (crGT), rodent assay of risky choice which wins are accompanied by salient cues. Both compounds also decreased impulsive premature responding. Objective The key neural loci mediating these effects were unknown. lateral orbitofrontal cortex (lOFC) medial prefrontal (mPFC), highly implicated assessment, action selection, impulse control, receive dense noradrenergic innervation. therefore infused atomoxetine guanfacine directly into either lOFC or prelimbic (PrL) mPFC prior to performance. Results When lOFC, improved decision making score adaptive lose-shift behaviour males, but not females, without altering motor impulsivity. Conversely, intra-PrL control preferring animals sexes, did alter making. Guanfacine administered PrL, altered impulsivity all subjects, though opposite direction atomoxetine. Conclusions These data highlight double dissociation between behavioural signaling across frontal regions with respect action. Given influence manipulations could depend baseline preference, suggest system may function differently subjects susceptible risk-promoting lure win-associated

Язык: Английский

Процитировано

8
Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex DOI
Tristan Hynes, Chloe S. Chernoff, Kelly M. Hrelja

и другие.

Biological Psychiatry, Год журнала: 2023, Номер 95(3), С. 220 - 230

Опубликована: Сен. 9, 2023

Язык: Английский

Процитировано

6
Pramipexole Hyperactivates the External Globus Pallidus and Impairs Decision-Making in a Mouse Model of Parkinson’s Disease DOI Open Access
Hisayoshi Kubota, Xinzhu Zhou, Xinjian Zhang

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8849 - 8849

Опубликована: Авг. 14, 2024

In patients with Parkinson's disease (PD), dopamine replacement therapy D2/D3 receptor agonists induces impairments in decision-making, including pathological gambling. The neurobiological mechanisms underlying these adverse effects remain elusive. Here, a mouse model of PD, we investigated the D3 (D3R)-preferring agonist pramipexole (PPX) on decision-making. PD mice were generated using bilateral injection toxin 6-hydroxydopamine into dorsolateral striatum. Subsequent treatment PPX increased disadvantageous choices characterized by high-risk/high-reward touchscreen-based Iowa Gambling Task. This effect was blocked selective D3R antagonist PG-01037. treated PPX, number c-Fos-positive cells external globus pallidus (GPe), indicating dysregulation indirect pathway corticothalamic-basal ganglia circuitry. accordance, chemogenetic inhibition GPe restored normal c-Fos activation and rescued PPX-induced choices. These findings demonstrate that hyperactivation neurons impairs decision-making mice. results provide candidate mechanism therapeutic target for gambling observed during pharmacotherapy patients.

Язык: Английский

Процитировано

2
Imaging of impulse control disorders in Parkinson's disease DOI
Stéphane Prange, Stéphane Thobois

Revue Neurologique, Год журнала: 2024, Номер 180(10), С. 1078 - 1086

Опубликована: Сен. 27, 2024

Язык: Английский

Процитировано

2
Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats DOI Creative Commons
Brett A. Hathaway, Andrew Li,

Hannah G. Brodie

и другие.

European Journal of Neuroscience, Год журнала: 2024, Номер 59(7), С. 1621 - 1637

Опубликована: Фев. 19, 2024

Abstract Deficits in cost/benefit decision making is a critical risk factor for gambling disorder. Reward‐paired cues may play an important role, as these stimuli can enhance preference rats. Despite extensive research implicating the dorsal striatum compulsive aspects of addiction, role nigrostriatal dopaminergic activity cue‐induced remains unclear, particularly females. Accordingly, we examined effects manipulating pathway on risky choice female TH:Cre rats were trained cued version rat Gambling Task. This task was designed such that maximal reward attained by avoiding high‐risk, high‐reward options and instead favouring associated with lower per‐trial gains, they feature less frequent shorter time‐out penalties. Adding reward‐paired audiovisual to leads greater average. To assess pathway, viral vector carrying either Cre‐dependent inhibitory or excitatory DREADD infused into substantia nigra. Rats then received clozapine‐N‐oxide during acquisition after stable performance baseline reached. Inhibition this accelerated development early sessions increased performance, but long‐term inhibition actually improved making. Activation had minimal effects. These results provide evidence involvement females, therefore shedding light its decision‐making deficits expanding our knowledge system.

Язык: Английский

Процитировано

0
The neuropharmacological profile of interval responding during operant tasks DOI
Robert Lalonde, C. Strazielle

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер 397(10), С. 7551 - 7560

Опубликована: Май 30, 2024

Язык: Английский

Процитировано

0
Clinical management model for impulse control disorders in Parkinson’s disease DOI Open Access
Han Li,

Yong Yang,

Liying Yang

и другие.

CNS Spectrums, Год журнала: 2024, Номер unknown, С. 1 - 10

Опубликована: Окт. 29, 2024

Abstract Over the last decade, we have gained a better understanding of impulse control disorder in Parkinson’s disease (PD-ICD), medication complication PD. Researchers were aware its complexity and took efforts to learn more about diagnostic treatment possibilities. Nevertheless, clinical management for it is currently neglected. We conducted narrative overview literature published from 2012 October 2023 on various aspects PD-ICD. A potential “susceptibility-catalytic-stress” model development PD-ICD was proposed profile encoding predictors created. Based these predictors, some methods prediction recently developed prediction, such as polymorphic dopamine genetic risk score clinic-genetic ICD-risk score. variety options, including dose reduction receptor agonists (DAs), DAs removal, switch, add-on therapy, are investigated with inconsistent reports. current findings, prototype centered prevention, consisting follow-up monitoring, recurrence reference, further 4 key principles, standardization, centered, persistence, whole course.

Язык: Английский

Процитировано

0