Incentive Cocaine‐Seeking Habits and Their Compulsive Manifestation Emerge After a Downregulation of the Dopamine Transporter in Astrocytes Across Functional Domains of the Striatum

European Journal of Neuroscience, Год журнала: 2025, Номер 61(5)

Опубликована: Март 1, 2025

ABSTRACT The development of compulsive cue‐controlled‐incentive drug‐seeking habits is a hallmark substance use disorder that predicated on an intrastriatal shift in the locus control over behaviour from nucleus accumbens (Nac) core–dorsomedial striatum network to Nac core–anterior dorsolateral (aDLS) network. This paralleled by drug‐induced (including cocaine) dopamine transporter (DAT) alterations originating ventral spread eventually encompass aDLS. Having recently shown heroin self‐administration results pan‐striatal reduction astrocytic DAT precedes aDLS dopamine‐dependent incentive heroin‐seeking habits, we tested hypothesis similar adaptations occur following cocaine exposure. We compared protein levels whole tissue homogenates, and astrocytes cultured dorsal striatal territories drug‐naïve male Sprague–Dawley rats those with history taking or cocaine‐seeking habit. Cocaine exposure resulted decrease across all striatum. further demonstrated (i.e., punishment‐resistant) were associated mRNA shell, but not core‐aDLS habit system. Together recent evidence heroin‐induced downregulation DAT, these findings suggest may represent common mechanism underlying drug classes.

Язык: Английский

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Neurostimulation to improve cognitive flexibility

Current Opinion in Behavioral Sciences, Год журнала: 2025, Номер 62, С. 101484 - 101484

Опубликована: Фев. 6, 2025

Язык: Английский

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Therapeutic potential of Baicalin against experimental obsessive compulsive disorder: Evidence from CSF, blood plasma, and brain analysis

Journal of Neuroimmunology, Год журнала: 2025, Номер unknown, С. 578598 - 578598

Опубликована: Март 1, 2025

Язык: Английский

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Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome

Journal of Psychiatric Research, Год журнала: 2025, Номер 182, С. 122 - 131

Опубликована: Янв. 7, 2025

Язык: Английский

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Grey and White Matter alterations in Obsessive-Compulsive Personality disorder: a Data Fusion Machine Learning approach

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Obsessive-Compulsive Personality Disorder (OCPD) is a complex mental condition marked by excessive perfectionism, orderliness, and rigidity, often starting in adolescence or early adulthood; it affects 1.9–7.8% of the population. The disorder differs from (OCD) for an apparent compromise personality, distorted self-representation altered perception others. Although two disorders present evident differences, unlike OCD, neural bases OCPD are understudied. few studies conducted so far have identified grey matter alterations brain regions such as striatum prefrontal cortex, but comprehensive model its neurobiology, eventual contribution white abnormalities, still unclear. One intriguing hypothesis that ascribed to Default Mode Network involved OCPD, similar what has been shown OCD other anxiety disorders. To test this hypothesis, images 30 individuals diagnosed with (73% female, mean age = 29.300), 34 healthy matched controls (82% 25.599) were analyzed data fusion unsupervised machine learning method known Parallel Independent Component Analysis (pICA) detect joint these modalities diagnosis. Results indicated gray networks (GM5 GM23) one network (WM25) differed between control group. GM5 included belonging Salience Network, was significantly correlated anxiety; GM-23 portions cerebellum, precuneus, fusiform gyrus; WM-25 adjacent regions. These findings shed new light on contributions may pave way developing objective markers disorder.

Язык: Английский

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Local effective connectivity changes after transcranial direct current stimulation in obsessive-compulsive disorder patients

Journal of Affective Disorders, Год журнала: 2025, Номер 374, С. 116 - 127

Опубликована: Янв. 11, 2025

This study investigates the effects of transcranial direct current stimulation (tDCS) on brain network connectivity in individuals with obsessive-compulsive disorder (OCD). In a randomized, double-blind, sham-controlled experimental design anodal tDCS (vs. sham) was applied total 43 right-handed patients OCD, targeting right pre-supplementary motor area (pre-SMA). Cathodal reference electrode put left pre-SMA. The set as 2 mA, duration either 30 s (sham) or 1200 s. Concurrent resting-state functional MRI data were collected following (or stimulation. We employed regression dynamic causal modelling (rDCM) to extract whole effective (EC) matrices subsequently analyzing these through graph theory approaches examine changes activity across different scales. found that compared sham caused significant local connectivity. Increased recruitment level detectable sensorimotor (SMN), indicating enhanced intra-network after active tDCS. Clustering coefficient and efficiency also be increased same area. No regard global Current findings indicate single-session can effectively alter connectivities within SMN OCD patients. Given relevance connected regions for pathophysiology we believe areas might constitute an intervention normalize altered OCD. used single session, which may not reflect long-term effects.

Язык: Английский

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Zona incerta: from Parkinson's disease to addiction

Frontiers in Neural Circuits, Год журнала: 2025, Номер 19

Опубликована: Фев. 6, 2025

The zona incerta (ZI), a small and historically overlooked structure located beneath the thalamus, has been increasingly recognized for its role in diverse behavioral processes. Early studies 1970s 1980s explored ingestive behaviors, including drinking feeding (for review, see (Mitrofanis, 2005))(Figure 1a), suggesting involvement motivation survival mechanisms related to food water intake. ZI is now known be heterogeneous nucleus, divided into four major sectors: rostral (ZIr), dorsal (ZId), ventral (ZIv), caudal (ZIc) 2005), each with distinct neurochemical profiles. GABAergic cells, which constitute majority of ZI's neurons, parvalbumin positive neurons are mostly concentrated ZIv, while ZId rich glutamatergic ZIr contains dopaminergic 2005).While motor functions were identified as early 60s (Hyde Toczek, 1962), focus really shifted on those motor-related roles 1990s, became studied context Parkinson's disease (PD) (Shi et al., 2024). introduction deep brain stimulation (DBS) treatment PD patients, subthalamic nucleus (STN) primary target (Benabid 2009), revealed that stimulating nearby also produced significant improvements symptoms (Voges 2002) (Ossowska, 2020). This led renewed interest ZI, placing it spotlight movement disorder therapies. Consequently, non-motor functions, particularly potential reward processes driving behaviors previously characterized, received less attention. However, reports effects following patients-especially mood (Stefurak 2003) , (Tommasi 2008), or emotion (Burrows 2012)-suggested broader ZI. Notably, motivational alterations such apathy (Czernecki, 2005) (Ricciardi 2014) drew attention processes.Today, there link between motivation. contemporary approaches map, monitor manipulate neural circuits improving our understanding contribution different subregions neuronal populations constituting various functions. shares remarkable similarities substantia nigra pars compacta (SNc) tegmental area (VTA), terms their specific involvements behavior (Morales Margolis, 2017). While VTA, more recently SNc, intensively investigated motivation-related pathologies, especially addiction, this aspect remains largely unexamined. Addiction chronic psychiatric defined by loss control over drug intake, despite negative consequences. It involves recurrent periods seeking, withdrawal relapse, leading spiraling addiction cycle (Koob Le Moal, 2008) Volkow, 2010). Recent findings raise new questions about behaviors. short essay examines current evidence disorders akin highlights future research directions.While underexplored, pharmacological support responsiveness drugs abuse. In situ alcohol injection elicits strong responses (Wayner 1975), injections tetrahydropapaveroline, used initiate consumption rats when injected mesocorticolimbic pathway, induces preference (Myers Privette, 1989). Cocaine intake impacts well, increasing Fos expression (Zahm 2010) reducing neurotensin binding, paralleling pathways (Pilotte 1991). Furthermore, morphine tyrosine hydroxylase enhances dopamine (DA) metabolism implicating modulation (Molnar 1994). These indicate abuse directly impact activity, supporting relevance research.The critical features VTA SNc. A first notable parallel 3 structures presence neurons. Dopaminergic transmission from SNc instrumental at core disorders. All trigger DA release striatum, accumbens (NAc) (Di Chiara Imperato, 1988), signaling values valence biologically relevant stimuli (Bromberg-Martin (Schultz, 1998), but encoding prediction errors (RPE) guide learning (Hollerman Schultz, 1998) making mesolimbic nigrostriatal fundamental motivated (Berke, 2018). Alterations these contribute addiction-like excessive seeking taking (Keiflin Janak, 2015) (Goutaudier 2023) (Giuliano 2019) 1997). Very few have focused (ZIDA), recent suggest pivotal (Ye 2023), Specifically, ZIDA overactive during energy deficit, promoting food-seeking maintaining behavior, partly through projections paraventrical thalamus (PVT) 2023). Moreover, seem involved other appetitive self grooming (Jiang Increased observed abstinence, reflecting sociability impairments models (Lalanne 2017) (Homberg stereotypical induced psychostimulants exacerbated drug-sensitization (Kalueff 2016). Excessive marker compulsivity rodent obsessivecompulsive (Mondragón-González consistent connectivity data both human non-human primates highlighted treating obsessive-compulsive (ICDs) (Haber 2023).In addition well-studied contain substantial populations, another feature common Similar (Zhou 2022) (Lowes 2021), (ZIGABA) regulate project NAc (Wang Their optogenetic shown provoke binge-like eating mice, ablation decreases long-term, reduction body weight result (Zhang Van Den Pol, Other types involve ZIGABA, example hunting (Zhao 2019), novelty (Monosov (Ogasawara 2022), trait particular field an endophenotype vulnerability, predicting transition controlled compulsive cocaine use (Belin Deroche-Gamonet, 2012). Optogenetic activation ZIGABA favor exploration objects conspecifics (Ahmadlou 2021). As NAc-projecting undergo activity changes synaptic plasticity exposure (Friend 2021) (Williams 2018), motivation(Ting-A-Kee 2013) (Elum 2024) (Merkel 2024), one can hypothesize neuroadaptations within ZIGABA-NAc circuit may similarly underlie aspects drug-seeking notably disinhibition exploratory toward novel elements environment.Collectively, exposed above highlight point out reinforcement drives phases eventually leads later marked abstinence individuals experience dysphoria, apathy, anxiety, depression pain. likely craving, process whereby sought consumed alleviate affect experienced 1997) (Robbins Beyond motivation, reminiscent state, anxiety (Li pain (Lu implicated aversive connections amygdala thalamic periaqueductal grey (Chou 2018) (Venkataraman Thus, multifaceted posit contributor addiction.Taken together, all withdrawal-related drug-seeking, become evident positioning canonical (Lüscher 2021)(Figure 1b). structural two circuits. bidirectionally connected and, lesser extent, projects NAc, ideally situated modulate midbrain striatum (Arena mentioned above, PVT key player receives inputs prefrontal cortex lateral hypothalamus (Iglesias Flagel, Zhu, 2019). do not provide input 2014), could play modulatory role, linking homeostatic reward-driven processes, modulating indirectly. aligns decrease striatal after electrolytic lesion (Walker Finally, several nuclei cortex, amygdala, habenula (Figure strategically positioned numerous processes.Overall, clear still emerging, addiction-related circuits, pathways, emotion, interoception, theoretical addiction. potentially recapitulating certain extent some VTA/SNc obviously argument underpinning opinion precise discussed, others found no alteration manipulating cell population, limited prehensile (Garau stark contrast place instance. seems widely accepted, distinction GABA must however put perspective, purely co-express neurotransmission markers (Negishi considerations, remain unanswered: Does induce ZI? encode RPE well? Do adaptations drive escalation, symptoms, seeking? Investigating clarify therapeutic relevance. intersection offers intriguing perspectives, only disorders, clinical ICDs, gambling, hypersexuality, eating, prevalent (Houeto 2016) (Leclercq Corvol, resume most psychobiological (Vassileva Conrod, They attributed replacement therapy 2016), pathological underpinnings fully characterized (Prange Thobois, might ZIDA. Interestingly, L-DOPA parkinsonian (Cole 1993) (Bastide hypothesis.ICDs globally well alleviated STN-DBS patients (Scherrer Given anatomical proximity STN suppression ZI-DBS (Mallet 2002), benefit DBS applied neurological (Vorspan (Pelloux Baunez, 2013), considering ICDs (Potenza, emerge avenue addictions. side associated 2020) need investigations delineate sectors optimize strategies.Figure 1: Zona Incerta interest's evolution, function addiction? (A) Evolution topics publications (ZI) 1965 2024. Data obtained bibliometric analysis scientific literature PubMed, articles "zona incerta" title ; primarily tracing, anatomy, cytoarchitecture, neurodevelopment excluded, even if they referenced (n = 213 articles). Bars represent number per decade, main functional thematic categories: (light blue), (medium deep-brain (dark (orange), threat stress-related (green), somatosensory (red), sexual hormones (pink), (yellow), (grey). emphasized started shift 1990s PD, 2010s tremendous increase last years, resurgence (B) Position mediating represented; simplified adapted Luscher 2021. structures, node Amg: Amygdala, DS: Dorsal Striatum, NAc: Nucleus Accumbens, LHb: Lateral Habenula, mPFC: medial Prefrontal Cortex, PVT: ParaVentricular Thalamus, SNc: Substantia Nigra Compacta, vHipp: Hippocampus, VP: Ventral Pallidum, Tegmental Area, ZI: Incerta.

Язык: Английский

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Pathomechanisms of neuropsychiatric disturbances in atypical parkinsonian disorders: a current view

Journal of Neural Transmission, Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Язык: Английский

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A Roadmap for Transformative Translational Research on Gambling Disorder in the UK Funded by A New Levy on The Gambling Industry

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

Опубликована: Фев. 1, 2025

Язык: Английский

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Understanding disrupted motivation in Parkinson’s disease through a value-based decision-making lens

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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