Paraventricular thalamus to nucleus accumbens circuit activation decreases long-term relapse of alcohol-seeking behaviour in male mice.

BACKGROUND: Some studies have highlighted the crucial role of aversion in addiction treatment. The pathway from the anterior paraventricular thalamus (PVT) to the shell of the nucleus accumbens (NAc) has been reported as an essential regulatory pathway for processing aversion and is also closely associated with substance addiction. However, its impact on alcohol addiction has been relatively underexplored. Therefore, this study focused on the role of the PVT-NAc pathway in the formation and relapse of alcohol addiction-like behaviour, offering a new perspective on the mechanisms of alcohol addiction. RESULTS: The chemogenetic inhibition of the PVT-NAc pathway in male mice resulted in a notable decrease in the establishment of ethanol-induced conditioned place aversion (CPA), and NAc-projecting PVT neurons were recruited due to aversive effects. Conversely, activation of the PVT-NAc pathway considerably impeded the formation of ethanol-induced conditioned place preference (CPP). Furthermore, during the memory reconsolidation phase, activation of this pathway effectively disrupted the animals' preference for alcohol-associated contexts. Whether it was administered urgently 24 h later or after a long-term withdrawal of 10 days, a low dose of alcohol could still not induce the reinstatement of ethanol-induced CPP. CONCLUSIONS: Our results demonstrated PVT-NAc circuit processing aversion, which may be one of the neurobiological mechanisms underlying aversive counterconditioning, and highlighted potential targets for inhibiting the development of alcohol addiction-like behaviour and relapse after long-term withdrawal.

The effects of alcohol tax policies on alcohol consumption and alcohol use disorders in Mainland of China: an interrupted time series analysis from 1961-2019.

Background: Overwhelming evidence suggests that increasing alcohol taxes is an effective strategy for curbing alcohol consumption. However, research on the effects of such strategies in low- and middle-income nations is limited.Objective: The aim is to explore the temporal effect of alcohol tax policy in China.Methods: We employ interrupted time series analysis to investigate the temporal effects of tax policy changes on alcohol consumption and related consequences in Mainland China from 1961 to 2019. The study population, the total population of mainland region of China, aged more than 15 years.Results: The results show that the volume tax policy, which was announced in 2000 and implemented in 2001, led to an immediate reduction in the alcohol consumption (coefficient = -0.429, p < .001). Following the implementation of higher alcohol taxes in 1998 and 2001, the prevalence of alcohol use disorders (AUDs) and related years lived with disability (YLDs) gradually decreased. The relaxation of tax policy in 2006 led to a significant increase in alcohol consumption, both immediately (coefficient = 0.406, p < .001) and in the middle term (coefficient = 0.495, p < .001), as well as contribute to an immediate or medium term significant increase in the prevalence of AUDs (coefficient = 0.038, p = .010; coefficient = 0.032, p < .001) and YLDs (coefficient = 4.363, p = .001; coefficient = 4.226, p < .001).Conclusion: This study demonstrates that changes in alcohol consumption and related consequences (increase or decrease) have followed corresponding changes in alcohol tax policies (easing or tightening), indicating that increasing alcohol taxes can be an effective strategy in China for controlling alcohol consumption and related harms.

Mitochondrial Damage of Lymphocytes in Patients with Acute Relapse of Schizophrenia: A Correlational Study with Efficacy and Clinical Symptoms.

Objective: Accumulating evidence has demonstrated that schizophrenia is associated with mitochondrial and immune abnormalities. In this pilot case-control study, we investigated the level of mitochondrial impairment in lymphocytes in patients with acute relapse of schizophrenia and explored the correlation between the level of mitochondrial damage and symptoms or treatment response. Methods: Lymphocytic mitochondrial damage was detected using mitochondrial fluorescence staining and flow cytometry in 37 patients (at admission and discharge) and 24 controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale (CGI-S). Results: The levels of mitochondrial damage in CD3+ T, CD4+ T, and CD8+ T lymphocytes of the patients with schizophrenia at admission were significantly higher than those of the controls (p<0.05) and did not return to normal at discharge (p>0.05). The mitochondrial damage of T cells significantly improved at discharge for responsive patients only, as compared with that at admission (P<0.05). However, no significant difference was found in mitochondrial damage in CD19+ B cells between patients and healthy controls, or between admission and discharge (p>0.05). Furthermore, the reduction in mitochondrial damage of CD3, CD4, and CD8 lymphocytes was positively correlated with the reduction of the score of the PANSS positive scale at discharge (p<0.05), while no significant correlation was found between the level of mitochondrial damage in lymphocytes and the scores of PANSS and CGI-S. Conclusion: Acute relapse of schizophrenia might be associated with higher levels of mitochondrial damage in peripheral blood T lymphocytes. The degree of recovery of mitochondrial impairment in the T cells may be used as a predictor of treatment response in schizophrenia. As this is a pilot study, the conclusion still needs further verification in large-scale studies.

Reduction of Orexin-A Is Associated With Anxiety and the Level of Depression of Male Methamphetamine Users During the Initial Withdrawal Period.

Background: Orexin has been linked to the regulation of reward and motivation in animals, but there have been few human studies to validate its regulatory effects. We aimed to determine how orexin-A levels changed during different stages of withdrawal, as well as the relationship between orexin-A levels and withdrawal symptoms in male METH users. Methods: This study included 76 METH users and 35 control participants. The METH users were divided into three groups: group 1 (abstinence within 1 week, n = 23), group 2 (abstinence between 1 week and 3 months, n = 38), and group 3 (abstinence over 3 months, n = 15). At baseline and 1 month of enrollment, the plasma orexin-A level was examined. To track the withdrawal symptoms, self-report questionnaires (anxiety, depression, craving, and sleep quality) were collected at two points. Results: The orexin-A levels of groups 1 (p < 0.001) and 2 (p < 0.001) were lower than that of the controls at baseline but not group 3. One month later, the orexin-A levels of group 2 (p < 0.05) significantly increased, while no significant changes in those of groups 1 and 3 were observed. Furthermore, the orexin-A levels of group 1 were positively linked with depression (p < 0.01) and anxiety (p < 0.01) at baseline. Conclusions: The decrease in orexin-A levels was only transitory during the initial abstinence phase, and it was eventually restored near to normal with continued abstinence among the male METH users. Furthermore, a lower concentration of orexin-A may serve as a risk factor for negative emotions during METH withdrawal.

The transition of alcohol control in China 1990-2019: Impacts and recommendations.

The harmful use of alcohol is a severe public health issue globally. Chinese per-capita alcohol consumption has increased sharply in recent decades, which has contributed to a rise in alcohol-related problems. In this article we present an analysis of Chinese alcohol policy, beginning with a characterization of alcohol consumption in China followed by an examination of how the nation's alcohol control policy has evolved over the past 30 years, identifying shortcomings and obstacles to improvement. Finally, we present several recommendations informed by the Global Strategy to Reduce the Harmful Use of Alcohol and the SAFER Technical Package-Five Areas of Intervention at National and Subnational Levels (SAFER initiative), to the areas of taxation, alcohol availability, alcohol marketing regulation, and treatment.