Neurotransmitters crosstalk and regulation in the reward circuit of subjects with behavioral addiction

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

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Real-time activity of dynorphin-expressing neurons in mouse central amygdala during alcohol drinking

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

Published: Feb. 21, 2024

Alcohol use disorder (AUD) is a chronic disease that poses significant economic burden and health risks. It pivotal to better understand brain mechanisms engaged by alcohol promote misuse. The central amygdala (CeA) has emerged as key mediator of excessive preclinical consumption. A dynorphin-expressing subpopulation within the CeA (CeA Dyn ) been implicated in drinking, yet how cellular activity neurons relates ongoing drinking not well-understood. current study interrogated engagement male female mice during voluntary consumption using fiber photometry compared this response with other solutions having similar motivational and/or taste characteristics. Activity calcium sensor, GCaMP7f, expressed mouse was recorded time-locked bouts drinking. Multilevel linear mixed modeling applied resolve focal effects from complex data. These analyses revealed relatively large increase neuron transients after water or sucrose indicating these are uniquely Drinking behavior unique (i.e., longer bout durations) did fully explain signal differences between nor increased diminish over time. No conditions tested reproduced pronounced change associated findings, collectively, support presence functional signature for cell population known control Central dynorphin cells firmly higher when drank versus solutions. Neither states could activity. high responses may underlie AUD development.

Language: Английский

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Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 22, 2024

Abstract Alcohol use disorder (AUD) is frequently comorbid with anxiety disorders, yet whether alcohol abuse precedes or follows the expression of remains unclear. Rodents offer control over first drink, an advantage when testing causal link between and AUD. Here, we utilized a risk-avoidance task to determine anxiety-like behaviors before after exposure. We found that alcohol’s anxiolytic efficacy varied among inbred mice high showed heightened relief. While dopamine D1 receptors in striatum are required for relief, their levels alone were not correlated Rather, ratio striatal D2 was determinant factor show increasing receptor sufficient promote enhance even at initial Mice more prone continue drinking despite adverse effects, hallmark These findings suggest phenotype may be predisposing

Language: Английский

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Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from chronic binge alcohol

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

Published: Nov. 26, 2024

Abstract Proinflammatory microglial activation and hyperkatifeia during withdrawal are key features or Alcohol Use Disorder (AUD) as well in rodent models of binge alcohol. However, it is unclear the role microglia play development AUD behavioral phenotypes, particularly negative affect hyperkatifeia. We hypothesized proinflammatory promote neuronal death prolonged abstinence. METHODS: Inflammatory affective responses were measured adult mice 24h 4 weeks after 10 daily ethanol exposures (5g/kg/d, i.g.). RT-PCR was used to measure expression pro-inflammatory genes. FosB immunohistochemistry stress circuitry central amygdala (CeA), BNST, infralimbic cortex (IL) a proxy for activity. Behavioral testing performed additional cohorts anxiety-like behavior (center time open field), hyperarousal (acoustic startle), inflexible (conditioned fear memory with extinction). To determine microglia, Gi DREADDs activated (CX3CR1.CreERT2.hm4di+/-EtOH +/- CNO). RESULTS: Binge increased gene both EtOH lasting into (type I IFNs). Ten binges while simultaneously reducing BDNF persistently dBNST CeA. Ethanol-treated spent less center field (anxiety-like behavior), had magnitude acoustic startle reflex (hyperarousal) reduced extinction conditioned (PTSD phenotype) 4-5 Gi-DREADD inhibition alcohol treatment blocked persistent increases cytokines, prevented ethanol-induced (TUNEL), including memory. CONCLUSION: These data find causative behaviors withdrawal. The prevention these effects by reveals integral acute on pathogenesis.

Language: Английский

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