Addiction Biology最新文献

We are writing to express our insights and reflections on the recently published study by Fathi et al.,¹ ‘Video game addiction is associated with early stage of inhibitory control problems: An event-related potential study using cued Go/NoGo task’, in your esteemed journal. This groundbreaking research offers valuable evidence linking video game addiction (VGA) to early-stage inhibitory control issues, employing a cued Go/NoGo task to examine brain activity related to response inhibition.

Drawing from our experience and the context of similar research in Taiwan, we find this study's approach and findings both compelling and significant. For instance, a study on ‘Wisdom and the Net-Entangled Generation: Discussing the Cooperation between Parents and Teachers in Addressing Adolescents' Mobile Internet Addiction’ in Taiwan² also addresses the challenges posed by digital addiction among youth, suggesting the importance of collaborative efforts between parents and educators to mitigate the issue. These concerns echo the findings of Fathi et al., reinforcing the global relevance of understanding and addressing the cognitive impacts of digital addictions.

Furthermore, the study's use of event-related potentials (ERPs) to explore the neural underpinnings of inhibitory control issues in individuals with VGA is remarkably insightful. It mirrors a broader academic interest in applying neuroscientific methods to study behavioural addictions. For example, the research by Chen³ on the integration of digital games in English vocabulary teaching hints at the nuanced interactions between digital media usage and cognitive processes, underscoring the need for balanced approaches in digital consumption.

It is also worth noting that Fathi et al.'s identification of specific ERP components (e.g., reduced N2 amplitude) provides a concrete neural basis for understanding the cognitive impairments associated with VGA. This aligns with trends in educational and psychological research that seek to identify the physiological and cognitive impacts of technology use among adolescents.⁴

While Fathi et al.'s study focuses on the early-stage inhibitory control problems, it prompts further investigation into long-term cognitive and social outcomes of VGA. It raises questions about the effectiveness of interventions and educational programs designed to mitigate these effects. The Taiwanese context, with its diverse approach to addressing digital and gaming addictions, offers a rich ground for comparative studies that could further elucidate the mechanisms and outcomes of such interventions.

In conclusion, Fathi et al.'s study is a significant contribution to the burgeoning field of research on digital addictions and their cognitive impacts. It underscores the urgency of developing informed, multi-faceted strategies to address these issues. By integrating

Dr. Kelly Dunn and colleagues have published an intriguing exploration of heterogeneity and individual differences in the affective and side effects of opioids.¹ Their analysis is based on a rich psychopharmacological dataset in which 100 healthy volunteers received four doses of hydromorphone and placebo over five test days. It is vital and urgent that we understand how these pain management medications affect individuals to identify risks.

The debate on how opioids affect the experience of pleasure and pain has roots at least as far back as 1925, when Lorenz Kolb shared his observation that opioids rarely caused pleasure (as opposed to relief) in ‘any one except the emotionally unstable, the psychopath or the neurotic’ (p. 699).² After the development of randomized controlled trials, a seminal 1955 study measured the effects of double-blinded doses of morphine and heroin, among other drug classes, in 20 healthy male college students. The average response to opioids was not pleasure, but dysphoria.³

This early conclusion was not supported in a more nuanced investigation, however. Based on qualitative interviews with heroin-addicted individuals, observations of college students trying heroin for the first time, and a reanalysis of the 1955 RCT data, MacAuliffe⁴ argued that a significant minority of participants did report positive effects from opioids. He also provided evidence that negative initial responses to heroin were frequent in addicted populations, but that social support within groups of addicted individuals promoted perseverance (through several injections of heroin) until the opioid's desirable effects outweighed the initial nausea and vomiting it caused.

In the recent paper, Dunn and colleagues draw inspiration from the alcohol literature, where people with minimal responses to early drinking have been reported to have a higher risk of developing problematic alcohol use. They also draw on findings related to variation in the mu-opioid receptor gene, specifically the A118G polymorphism. Despite initial high expectations and early evidence linking the polymorphism to differential alcohol and nicotine responses,⁵ relatively few studies have examined the impact of A118G on acute opioid effects.⁶ The scarce evidence likely relates to increasing recognition that the explanatory value of individual genetic polymorphisms is typically insufficient for an average-sized drug study.

Inspired by Dunn et al.’s findings, we briefly revisited our own unpublished drug effects data relating to this polymorphism. In an early study on how opioids affect reward behaviours, we selected a high proportion of G allele carriers of this specific polymorphism.^{7, 8} A total of 49 healthy young men (27 AA and 22 G carriers) attended three sessions, where they receiv

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = −0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = −12.73, pFDR = 0.048) and posterior (B = −17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N-methyl-D-aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK/CREB signalling pathway in the NAc, are integral in regulating reward-seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR-D1R/ERK/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague–Dawley rats to establish a model of propofol self-administration behaviour. Subsequently, we microinjected D-AP5 (a competitive antagonist of NMDARs, 1.0–4.0 μg/0.3 μL/site) or vehicle into bilateral NAsh in rats that had previously self-administered propofol to examine the impact of NMDARs within the NAsh on propofol self-administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R/ERK/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D-AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1/2 (p-ERK1/2) and CREB (p-CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self-administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR-D1R/ERK/CREB signal transduction pathway.

Synthetic opioids such as fentanyl contribute to the vast majority of opioid-related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes. Here, we performed single nuclei RNA sequencing to study transcriptional programs in fentanyl-experienced mice. Male and female C57/BL6 mice self-administered intravenous fentanyl (1.5 μg/kg/infusion) or saline for 10 days. After 24 h abstinence, VTA nuclei were isolated and prepared for sequencing on the 10× platform. We identified different patterns of gene expression across cell types. In dopamine neurons, we found enrichment of genes involved in growth hormone signalling. In dopamine-glutamate-GABA combinatorial neurons, and some GABA neurons, we found enrichment of genes involved in Pi3k-Akt signalling. In glutamate neurons, we found enrichment of genes involved in cholinergic signalling. We identified transcriptional regulators for the differentially expressed genes in each neuron cluster, including downregulated transcriptional repressor Bcl6, and upregulated transcription factor Tcf4. We also compared the fentanyl-induced gene expression changes identified in mouse VTA with a published rat dataset in bulk VTA, and found overlap in genes related to GABAergic signalling and extracellular matrix interaction. Together, we provide a comprehensive picture of how fentanyl self-administration alters the transcriptional landscape of the mouse VTA that serves as the foundation for future mechanistic studies.

Impaired decision-making is often displayed by individuals suffering from gambling disorder (GD). Since there are a variety of different phenomena influencing decision-making, we focused in this study on the effects of GD on neural and behavioural processes related to loss aversion and choice difficulty. Behavioural responses as well as brain images of 23 patients with GD and 20 controls were recorded while they completed a mixed gambles task, where they had to decide to either accept or reject gambles with different amounts of potential gain and loss. We found no behavioural loss aversion in either group and no group differences regarding loss and gain-related choice behaviour, but there was a weaker relation between choice difficulty and decision time in patients with GD. Similarly, we observed no group differences in processing of losses or gains, but choice difficulty was weaker associated with brain activity in the right anterior insula and anterior cingulate cortex in patients with GD. Our results showed for the first time the effects of GD on neural processes related to choice difficulty. In addition, our findings on choice difficulty give new insights on the psychopathology of GD and on neural processes related to impaired decision-making in GD.

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction.

Neuronal ensembles in the medial prefrontal cortex mediate cocaine self-administration via projections to the nucleus accumbens. We have recently shown that neuronal ensembles in the prelimbic cortex form rapidly to mediate cocaine self-administration. However, the role of neuronal ensembles within the nucleus accumbens in initial cocaine-seeking behaviour remains unknown. Here, we sought to expand the current literature by testing the necessity of the cocaine self-administration ensemble in the nucleus accumbens core (NAcCore) 1 day after male and female rats acquire cocaine self-administration by using the Daun02 inactivation procedure. We found that disrupting the NAcCore ensembles after a no-cocaine reward-seeking test increased subsequent cocaine seeking, while disrupting NAcCore ensembles following a cocaine self-administration session decreased subsequent cocaine seeking. We then characterized neuronal cell type in the NAcCore using RNAscope in situ hybridization. In the no-cocaine session, we saw reduced dopamine D1 type neuronal activation, while in the cocaine self-administration session, we found preferential dopamine D1 type neuronal activity in the NAcCore.