Addiction Biology最新文献

This study employed network meta-analysis to evaluate the impact of several exercise interventions on mobile phone addiction. The aim is to determine the most effective exercise intervention measures and establish a reference for future intervention measures to improve mobile phone addiction. We systematically searched the relevant literature on the Web of Science, PubMed, Embase, Cochrane Library, China Knowledge, Wanfang and other domestic and foreign databases. We assessed the risk of bias according to the revised Cochrane Randomised Trial Bias Risk tool and performed traditional and Web-based meta-analyses using Review Manager 5.3 and Stata 14.0. The traditional meta-results showed that exercise intervention was superior to the control group in improving mobile phone addiction (SMD = −1.05, 95%CI −1.62, −0.48). Network meta-analysis results show that aerobic exercise (AE) is superior to other sports in reducing the total score of mobile phone addiction among teenagers, and the probability of aerobics becoming the best intervention for mobile phone addiction among teenagers is the highest (SUCRA = 95.6%). Exercise intervention can reduce the score of mobile phone addiction, while AE has more advantages in improving mobile phone addiction. However, due to the influence of sample size and the quality of the included literature, it is recommended that the results be further verified in the future.

Chronic nicotine administration leads to neuroadaptations, an important process in nicotine and tobacco dependence for which treatments are limited. The cysteine pro-drug, N-acetyl-cysteine (NAC), is a promising glutamatergic agent that has shown some clinical efficacy in reducing nicotine use in humans. The purpose of this study was to examine NAC in two rodent models of nicotine dependence. NAC (0, 5, 20, 50 and 100 mg/kg) was examined on locomotor activity in groups of rats previously exposed to nicotine or saline. In the second experiment, NAC (0, 50 and 100 mg/kg i.p.) was evaluated against the discriminative stimulus effects of nicotine (0.2 mg/kg) using a two-lever procedure under a tandem schedule (VI10”-FR10) of food reinforcement. Pre-treatment with NAC in doses greater than 20 mg/kg attenuated the expression of conditioned hyperactivity when rats were placed in locomotor boxes previously paired with chronic nicotine administration. The same doses of NAC had modest effects in attenuating nicotine-stimulated hyperactivity in nicotine-treated or saline-treated rats tested in the same locomotor boxes. In the discrimination task, NAC did not generalise to the nicotine stimulus and nor did it modify the dose–response curve to nicotine, suggesting that NAC may not modify the subjective effects of nicotine. These results suggest NAC selectively attenuates conditioned responses to nicotine-paired stimuli without modifying nicotine-induced hyperactivity or the discriminative stimulus effects of nicotine. Thus, the study proposes that if NAC was to act in a similar selective manner in humans, the specific action of NAC to attenuate conditioned responses may limit its potential as a treatment to manage nicotine dependence.

The rise of gaming-related content on social media has increased exposure to game-related stimuli, particularly among young people, which may reinforce gaming urges and create difficulties in controlling gaming behaviour. Therefore, understanding the management of gaming desire triggered by such content is critical. Identifying the neural mechanisms underlying resistance to these urges will be crucial for effective prevention and intervention. However, this issue has yet to be directly explored. The present study investigated the neural correlates of resisting gaming desire elicited by gaming-related social media videos using functional magnetic resonance imaging (fMRI). Young habitual online gamers participated in an fMRI study in which they viewed video stimuli under three conditions: (1) gaming cue condition: passive viewing of gaming-related videos; (2) gaming cue resist condition: viewing of gaming-related videos while actively resisting gaming desire; and (3) neutral cue condition. Gaming cues elicited significantly greater activation than neutral cues in the diverse brain areas including bilateral medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, posterior cingulate cortex (PCC), superior temporal gyrus (STG) and precuneus. Compared to the gaming cue condition, the gaming cue resist condition elicited increased activation in the left PCC and bilateral precuneus. Conversely, significant deactivation was observed in the right STG. These findings offer insights into the neural basis of craving resistance in response to social media-based gaming cues and may guide the development of targeted interventions for problematic gaming behaviour.

Adaptive stress coping is often impaired in individuals with alcohol use disorder (AUD). This process relies on neurocircuitry involved in emotional and behavioural regulation, particularly the ventromedial PFC (vmPFC) and orbitofrontal cortex (OFC), along with limbic and ventral striatal regions (e.g., amygdala, hippocampus and nucleus accumbens). These systems are highly sensitive to the neurotoxic effects of alcohol, which may disrupt their ability to flexibly adapt in response to acute stress. This study investigated state-dependent changes (termed ‘flexibility’) in vmPFC-limbic/striatal and OFC-limbic/striatal functional connectivity from rest to acute stress in individuals with AUD versus matched controls and examined associations with coping strategies. Twenty-four adults with AUD (age_mean = 33, 11F) and 23 matched controls (age_mean = 32, 11F) underwent fMRI during resting-state followed by the Montreal Imaging Stress Task (MIST) and completed the COPE Inventory. Functional connectivity between vmPFC-limbic/striatal and OFC-limbic/striatal regions was assessed during rest and stress (MIST) conditions. Group differences in state-dependent changes in functional connectivity were analysed using repeated-measures ANCOVA. Functional connectivity between the right OFC–right amygdala and right OFC–right hippocampus increased from resting-state to the MIST in the control group, but this shift was not present in the AUD group (group x condition, p_FDR < 0.05). Although connectivity did not differ between groups during the MIST (p's > 0.2), the AUD group exhibited elevated connectivity between these regions at rest (p's < 0.05). Moreover, among controls, increased right OFC–right hippocampus connectivity from rest to MIST was associated with more adaptive versus maladaptive coping (p < 0.05). Compared to controls, individuals with AUD exhibited a pattern of inflexible OFC-amygdala and OFC-hippocampus functional connectivity under changing stress conditions. Diminished stress-related connectivity changes in AUD appeared to be driven by elevated functional connectivity at rest. Future studies should test whether this resting-state connectivity pattern reflects an allostatic state that constrains the system's capacity to flexibly respond to acute stress.

Brain-derived neurotrophic factor (BDNF) and personality traits play a crucial role in the development of alcohol use disorder (AUD). However, the relationship between the BDNF gene, personality and AUD remains unclear. This study aimed to explore the role of BDNF gene variants, personality traits and impulsivity in both the presence of AUD and the age of onset of alcohol dependence. We also examined the interaction between BDNF gene variants and personality traits among individuals with AUD. Eleven polymorphisms encompassing the whole BDNF gene region were genotyped. The Tridimensional Personality Questionnaire (TPQ) and the Barratt Impulsiveness Scale-11 (BIS-11) assessed personality traits and impulsivity. Pearson's Chi-square, HAPLOVIEW software, logistic regression, independent t tests and linear regression were conducted to investigate the associations between BDNF variants, personality traits and impulsivity in patients with AUD. Five-hundred eighty-five AUD patients and 546 normal controls (NC) were recruited for the study. Although no polymorphisms were significantly associated with AUD after Bonferroni correction in gender- or age-stratified analyses, one specific haplotype block (TCA haplotype of rs1519480/rs6265/rs11030101) was related to AUD (p = 6.16 × 10⁻⁵). TPQ and BIS-11 results revealed that AUD patients, particularly those with early-onset AUD (EOAUD), exhibited significantly higher scores in Novelty Seeking (NS) and Harm Avoidance (HA) compared to NC. Additionally, the BDNF SNP rs6484320 was significantly associated with higher BIS-11 scores in the AUD group. High HA, NS, impulsivity, and the BDNF gene's specific haplotype may influence AUD's development. The findings may provide new insights into the genetic and psychological factors contributing to AUD.

Recent studies have established a strong association between the cerebellum and various psychiatric disorders, as well as drug addiction and withdrawal processes. However, the mechanisms underlying the cerebellum's role in nicotine withdrawal symptoms have yet to be explored. In this study, we employed transcriptome sequencing, untargeted metabolomics and integrative multi-omics analysis to elucidate the molecular mechanisms underlying nicotine withdrawal-induced affective symptoms, specifically anxiety and depression-like behaviours, within the cerebellum. Our findings demonstrate that enhanced purine metabolism and disrupted arginine metabolism in the cerebellum significantly contribute to the development of anxiety and depression-like behaviours in mice undergoing nicotine withdrawal. Treatment with the non-selective adenosine receptor antagonist, theobromine, markedly alleviates these behaviours. This mechanism likely involves inhibiting adenosine signalling and restoring arginine metabolism in the cerebellum.

Alcohol use disorder is closely related to genetic and environmental factors. However, the contribution of coding variation to alcohol use disorder susceptibility remains poorly understood. We aimed to identify genetic mutations in alcohol use disorder by whole exon sequencing. We performed whole-exome sequencing in 83 patients with alcohol use disorder and compared it with exome sequences of healthy controls that were collected from the 1000 Genomes Project. GO and KEGG enrichment analysis and protein interaction analysis were performed for the mutated genes in each group. Three online protein function prediction sites were used to predict whether SNPs/InDels cause protein coding changes. Further, we conducted a rare variant exploration. We identified 106 525 SNV and 19 826 InDel gene mutations in alcohol use disorder. In the healthy and alcohol use disorder groups, mutations in CNTNAP3, ZNF683, ALDPH2, CCHCR1, ZNF45 and ESRRA loci were found to be deleterious mutations in all three sites; CNTNAP3, ZNF683, ALDPH2, CCHCR1, ZNF45 and ESRRA may be potential targets for future precision treatment of alcohol use disorders, and further provide new ideas for drug development.

This preregistered study investigates whether altered grey matter volume (GMV) in the insula and ventromedial prefrontal/anterior cingulate cortex (vmPFC/ACC) - regions commonly implicated in substance use disorder (SUD) - is associated with the degree of substance use or with the severity of substance-related problems, two distinct but correlated facets of SUD. Baseline structural MRI and behavioural assessment of substance use, substance-related problems (i.e., DSM-5 disorder severity) and negative urgency were conducted in 134 (poly-)substance users. At 1-year follow-up, behavioral assessments were repeated in 120 participants. Linear regression analyses tested associations between GMV in predefined regions (insula, vmPFC and ACC) and (1) degree of use, (2) substance-related problems and (3) substance-related problems controlled for use. Mediation analyses tested whether negative urgency mediated the problem-specific associations. GMV in all regions negatively related to substance-related problems and use (p_BH < 0.05). Controlled for use, GMV in the insula and vmPFC (p_BH < 0.05) but not ACC (p_BH = 0.06) related to substance-related problems. Follow-up results revealed differential patterns, but when controlling for use, GMV reductions at baseline did not significantly relate to follow-up substance-related problems (insula: p_BH = 0.06; ACC/vmPFC: p_BH > 0.23). Negative urgency related to GMV in the vmPFC (p_BH = 0.02) and mediated the association between vmPFC volume and substance-related problems controlled for use (indirect effect: CI [−0.12, −0.02]). We demonstrate that smaller GMV in the vmPFC and insula specifically relates to substance-related problems beyond substance use, albeit with distinct predictive value for prospective symptom development. This highlights the importance of distinguishing between the two facets of SUD to understand why some substance users develop SUD.

Propofol is recognized as an addictive substance in both humans and animals. Increasing evidence suggests that the prelimbic cortex (PL) within the medial prefrontal cortex (mPFC), plays an important role in mediating drug addiction. In this study, we trained adult male Sprague–Dawley rats to establish a model of locomotor sensitization (LS). Moreover, optogenetic inhibition of glutamatergic neurons within the PL inhibited the LS of propofol, whereas optogenetic activation of glutamatergic neurons within the PL promoted the LS of propofol. This effect could be blocked by NBQX (a competitive AMPAR antagonist) pretreatment. Subsequently, a microinjection of NBQX (0.25-1 μg/0.3 μL/site) or saline was administered into the bilateral PL to further examine the impact of AMPARs on the LS of propofol. We found that NBQX pretreatment significantly inhibited both the distance and activity in sensitized rats. The expressions of GluA1 and GluA2 subunits of AMPARs, phosphorylated NR1 subunit of NMDARs, D1Rs, phosphorylated ERK and phosphorylated CREB within mPFC were statistically significantly decreased after NBQX pretreatment, whereas, the expressions of total ERK, total CREB and total NR1 subunit remained unchanged. This evidence verifies the instrumental role of AMPARs within the PL in mediating the LS of propofol, and the NMDAR-D1R/ERK/CREB signalling pathway may act as a potential mechanism.