Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol...Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.展开更多
Gaming disorder has become a significant issue in mental healthcare. While gaming is an important form of entertainment, excessive gaming may cause serious consequences for players. At present, there are still controv...Gaming disorder has become a significant issue in mental healthcare. While gaming is an important form of entertainment, excessive gaming may cause serious consequences for players. At present, there are still controversies in the academic community concerning the public health problems related to gaming disorder. This article attempts to expound the definition, epidemiology, aetiology, diagnosis, treatment and prevention of gaming disorder, in order to contribute to future conceptualization of gaming disorder.展开更多
In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online g...In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online gaming disorders,in the general public.Substance use disorder is a chronic recurrent brain disease characterised by strong cravings,high recurrence rates,and a high proportion of comorbidity of mental and physical disorders.1 Therefore,regular long-term therapeutic interventions are critical to preventing dm g relapses while maintaining withdrawal.展开更多
Drug addiction or substance use disorder(SUD),has been conceptualized as a three-stage(i.e.binge/intoxication,withdrawal/negative affect,and preoccupation/anticipation/craving)recurring cycle that involves complex cha...Drug addiction or substance use disorder(SUD),has been conceptualized as a three-stage(i.e.binge/intoxication,withdrawal/negative affect,and preoccupation/anticipation/craving)recurring cycle that involves complex changes in neuroplasticity,reward,motivation,desire,stress,memory,and cognitive control,and other related brain regions and brain circuits.Neuroimaging approaches,including magnetic resonance imaging,have been key to mapping neurobiological changes correlated to complex brain regions of SUD.In this review,we highlight the neurobiological mechanisms of these three stages of addiction.The abnormal activity of the ventral tegmental,nucleus accumbens,and caudate nucleus in the binge/intoxication stage involve the reward circuit of the midbrain limbic system.The changes in the orbitofrontal cortex,dorsolateral prefrontal cortex,amygdala,and hypothalamus emotional system in the withdrawal/negative affect stage involve increases in negative emotional states,dysphoric-like effects,and stress-like responses.The dysregulation of the insula and prefrontal lobes is associated with craving in the anticipation stage.Then,we review the present treatments of SUD based on these neuroimaging findings.Finally,we conclude that SUD is a chronically relapsing disorder with complex neurobiological mechanisms and multimodal stages,of which the craving stage with high relapse rate may be the key element in treatment efficacy of SUD.Precise interventions targeting different stages of SUD and characteristics of individuals might serve as a potential therapeutic strategy for SUD.展开更多
基金supported by the National Key Basic Research and Development Program(NKBRDP)of China(No.2009CB522000)the National Natural Science Foundation of China(No.30971050)+1 种基金the State Key Program of the National Natural Science of China(No.81130020)the Key Program on Basic Science of Henan Science and Technology Department(No.094200510005)
文摘Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.
基金grants from the National Key R&D Program of China(2017YFC1310400)the National Natural Science Foundation of China(81371465 and 81671324).
文摘Gaming disorder has become a significant issue in mental healthcare. While gaming is an important form of entertainment, excessive gaming may cause serious consequences for players. At present, there are still controversies in the academic community concerning the public health problems related to gaming disorder. This article attempts to expound the definition, epidemiology, aetiology, diagnosis, treatment and prevention of gaming disorder, in order to contribute to future conceptualization of gaming disorder.
基金This work was supported by the Program of Shanghai Academic Research Leader(17XD1403300)the Shanghai Key Laboratory of Psychotic Disorders(13DZ2260500)+1 种基金the Shanghai Intelligent Engineering Technology Research Center for Addiction and Rehabilitation(19DZ2255200)and the Shanghai Clinical Research Center for Mental Health(19MC1911100).
文摘In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online gaming disorders,in the general public.Substance use disorder is a chronic recurrent brain disease characterised by strong cravings,high recurrence rates,and a high proportion of comorbidity of mental and physical disorders.1 Therefore,regular long-term therapeutic interventions are critical to preventing dm g relapses while maintaining withdrawal.
基金This study was supported by grants from the Hunan Provincial Natural Science Foundation of China(2020JJ4794)the Science Innovation 2030–Brain Science and Brain-Inspired Intelligence Technology Major Project(2022ZD0211200).
文摘Drug addiction or substance use disorder(SUD),has been conceptualized as a three-stage(i.e.binge/intoxication,withdrawal/negative affect,and preoccupation/anticipation/craving)recurring cycle that involves complex changes in neuroplasticity,reward,motivation,desire,stress,memory,and cognitive control,and other related brain regions and brain circuits.Neuroimaging approaches,including magnetic resonance imaging,have been key to mapping neurobiological changes correlated to complex brain regions of SUD.In this review,we highlight the neurobiological mechanisms of these three stages of addiction.The abnormal activity of the ventral tegmental,nucleus accumbens,and caudate nucleus in the binge/intoxication stage involve the reward circuit of the midbrain limbic system.The changes in the orbitofrontal cortex,dorsolateral prefrontal cortex,amygdala,and hypothalamus emotional system in the withdrawal/negative affect stage involve increases in negative emotional states,dysphoric-like effects,and stress-like responses.The dysregulation of the insula and prefrontal lobes is associated with craving in the anticipation stage.Then,we review the present treatments of SUD based on these neuroimaging findings.Finally,we conclude that SUD is a chronically relapsing disorder with complex neurobiological mechanisms and multimodal stages,of which the craving stage with high relapse rate may be the key element in treatment efficacy of SUD.Precise interventions targeting different stages of SUD and characteristics of individuals might serve as a potential therapeutic strategy for SUD.