Showing papers on "Addiction published in 2010"
TL;DR: The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.
4,160 citations
TL;DR: Overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating, demonstrating that common hedonic mechanisms may underlie obesity and drug addiction.
Abstract: We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
1,317 citations
TL;DR: Although Internet-addicted individuals have difficulty suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for Internet addiction, and it is currently impossible to recommend any evidence-based treatment of Internet addiction.
Abstract: Background: Problematic Internet addiction or excessive Internet use is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding computer use and Internet access that lead to impairment or distress. Currently, there is no recognition of internet addiction within the spectrum of addictive disorders and, therefore, no corresponding diagnosis. It has, however, been proposed for inclusion in the next version of the Diagnostic and Statistical Manual of Mental Disorder (DSM). Objective: To review the literature on Internet addiction over the topics of diagnosis, phenomenology, epidemiology, and treatment. Methods: Review of published literature between 2000–2009 in Medline and PubMed using the term “internet addiction.Results: Surveys in the United States and Europe have indicated prevalence rate between 1.5% and 8.2%, although the diagnostic criteria and assessment questionnaires used for diagnosis vary between countries. Crosssectional studies on samples of patients report high comorbidity of Internet addiction with psychiatric disorders, especially affective disorders (including depression), anxiety disorders (generalized anxiety disorder, social anxiety disorder), and attention deficit hyperactivity disorder (ADHD). Several factors are predictive of problematic Internet use, including personality traits, parenting and familial factors, alcohol use, and social anxiety. Conclusions and Scientific Significance: Although Internet-addicted individuals have difficulty suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for Internet addiction. Due to the lack of methodologically adequate research, it is currently impossible to recommend any evidence-based treatment of Internet addiction.
723 citations
TL;DR: Neurophysiological studies reveal phasic dopamine signals that transmit information related predominantly but not exclusively to reward, which is more restricted and stereotyped than neuronal activity in most other brain structures involved in goal directed behavior.
Abstract: Previous lesion, electrical self-stimulation and drug addiction studies suggest that the midbrain dopamine systems are parts of the reward system of the brain. This review provides an updated overview about the basic signals of dopamine neurons to environmental stimuli. The described experiments used standard behavioral and neurophysiological methods to record the activity of single dopamine neurons in awake monkeys during specific behavioral tasks. Dopamine neurons show phasic activations to external stimuli. The signal reflects reward, physical salience, risk and punishment, in descending order of fractions of responding neurons. Expected reward value is a key decision variable for economic choices. The reward response codes reward value, probability and their summed product, expected value. The neurons code reward value as it differs from prediction, thus fulfilling the basic requirement for a bidirectional prediction error teaching signal postulated by learning theory. This response is scaled in units of standard deviation. By contrast, relatively few dopamine neurons show the phasic activation following punishers and conditioned aversive stimuli, suggesting a lack of relationship of the reward response to general attention and arousal. Large proportions of dopamine neurons are also activated by intense, physically salient stimuli. This response is enhanced when the stimuli are novel; it appears to be distinct from the reward value signal. Dopamine neurons show also unspecific activations to non-rewarding stimuli that are possibly due to generalization by similar stimuli and pseudoconditioning by primary rewards. These activations are shorter than reward responses and are often followed by depression of activity. A separate, slower dopamine signal informs about risk, another important decision variable. The prediction error response occurs only with reward; it is scaled by the risk of predicted reward. Neurophysiological studies reveal phasic dopamine signals that transmit information related predominantly but not exclusively to reward. Although not being entirely homogeneous, the dopamine signal is more restricted and stereotyped than neuronal activity in most other brain structures involved in goal directed behavior.
624 citations
TL;DR: Recent paradoxical data are discussed, which either support or oppose the hypothesis that drug- induced changes in dendritic spines drive addictive behavior, and areas where future investigation can provide a more detailed picture of drug-induced synaptic reorganization are defined.
597 citations
TL;DR: Many mental disorders are associated with an increased risk of later substance use conditions, but important differences in these associations are observed across the categories of use, abuse and dependence with abuse.
Abstract: Aims The comorbidity of mental disorders and substance dependence is well documented, but prospective investigations in community samples are rare. This investigation examines the role of primary mental disorders as risk factors for the later onset of nicotine, alcohol and illicit drug use, abuse and dependence with abuse. Design The National Comorbidity Survey (NCS) was a nationally representative survey of mental and substance disorders in the United States carried out in 1990–92. The NCS‐2 re‐interviewed a probability subsample of NCS respondents in 2001–03, a decade after the baseline survey. Participants A total of 5001 NCS respondents were re‐interviewed in the NCS‐2 (87.6% of baseline sample). Results Aggregate analyses demonstrated significant prospective risks posed by baseline mental disorders for the onset of nicotine, alcohol and illicit drug dependence with abuse over the follow‐up period. Particularly strong and consistent associations were observed for behavioral disorders and previous substance use conditions, as well as for certain mood and anxiety disorders. Conditional analyses demonstrated that many observed associations were limited to specific categories of use, abuse or dependence, including several mental disorders that were non‐significant predictors in the aggregate analyses. Conclusions Many mental disorders are associated with an increased risk of later substance use conditions, but important differences in these associations are observed across the categories of use, abuse and dependence with abuse. These prospective findings have implications for the precision of prevention and treatment strategies targeting substance use disorders.
506 citations
TL;DR: A novel theoretical framework for addiction is proposed in which the insula represents the interoceptive effects of drug taking, making this information available to conscious awareness, memory and executive functions.
Abstract: We have recently shown that damage to the insula leads to a profound disruption of addiction to cigarette smoking (Naqvi et al., Science 315:531-534, 2007). Yet, there is little understanding of why the insula should play such an important role in an addictive behavior. A broad literature (much of it reviewed in this issue) has addressed the role of the insula in processes related to conscious interoception, emotional experience, and decision-making. Here, we review evidence for the role of the insula in drug addiction, and propose a novel theoretical framework for addiction in which the insula represents the interoceptive effects of drug taking, making this information available to conscious awareness, memory and executive functions. A central theme of this framework is that a primary goal for the addicted individual is to obtain the effects of the drug use ritual upon the body, and representations of this goal in interoceptive terms by the insula contribute to how addicted individuals feel, remember, and decide about taking drugs. This makes drug addiction like naturally motivated behaviors, such as eating and sex, for which an embodied ritual is the primary goal.
503 citations
TL;DR: A key role is identified for MeCP2 in the dorsal striatum in the escalating cocaine intake seen in rats with extended access to the drug, a process that mimics the increasingly uncontrolled cocaine use seen in addicted humans.
Abstract: The X-linked transcriptional repressor methyl CpG binding protein 2 (MeCP2), known for its role in the neurodevelopmental disorder Rett syndrome, is emerging as an important regulator of neuroplasticity in postmitotic neurons. Cocaine addiction is commonly viewed as a disorder of neuroplasticity, but the potential involvement of MeCP2 has not been explored. Here we identify a key role for MeCP2 in the dorsal striatum in the escalating cocaine intake seen in rats with extended access to the drug, a process that mimics the increasingly uncontrolled cocaine use seen in addicted humans. MeCP2 regulates cocaine intake through homeostatic interactions with microRNA-212 (miR-212) to control the effects of cocaine on striatal brain-derived neurotrophic factor (BDNF) levels. These data suggest that homeostatic interactions between MeCP2 and miR-212 in dorsal striatum may be important in regulating vulnerability to cocaine addiction.
432 citations
TL;DR: Recent studies in mice involving deletion and replacement of nicotinic acetylcholine receptor subunits have begun to identify the molecular mechanisms underlying nicotine addiction and might offer new therapeutic strategies to treat this addiction.
Abstract: The past decades have seen a revolution in our understanding of brain diseases and in particular of drug addiction. This has been largely due to the identification of neurotransmitter receptors and the development of animal models, which together have enabled the investigation of brain functions from the molecular to the cognitive level. Tobacco smoking, the principal - yet avoidable - cause of lung cancer is associated with nicotine addiction. Recent studies in mice involving deletion and replacement of nicotinic acetylcholine receptor subunits have begun to identify the molecular mechanisms underlying nicotine addiction and might offer new therapeutic strategies to treat this addiction.
418 citations
TL;DR: Data indicate that impulsivity is a behavioral endophenotype mediating risk for stimulant dependence that may be exacerbated by chronic drug exposure, whereas abnormal sensation-seeking is more likely to be an effect of stimulant drug abuse.
408 citations
TL;DR: Evidence is provided for the value of incorporating mindfulness practice into substance abuse treatment and identifies a potential mechanism of change following Mindfulness-based relapse prevention.
Abstract: Addiction has generally been characterized as a chronic and relapsing condition (Connors, Maisto, & Zywiak, 1996; Leshner, 1999). Research on the relapse process has implicated numerous risk factors that appear to be the most robust and immediate predictors of posttreatment substance use, including negative affect, craving or urges, interpersonal stress, motivation, self-efficacy, and ineffective coping skills in high-risk situations (Connors et al.,1996; Witkiewitz & Marlatt, 2004). Targeting these risk factors during treatment, either pharmacologically (e.g., naltrexone to reduce alcohol craving; Richardson et al., 2008) or behaviorally (e.g., coping skills training; Monti et al., 2001), has become a priority for substance abuse researchers and clinicians.
TL;DR: A model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions is presented, which reflects decreased sensitivity of reward circuits, enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and a weakened control circuit.
Abstract: Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.
TL;DR: It is reported that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine, revealing new molecular regulators that control the complex actions of cocaine in brain reward circuitries and providing an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs.
Abstract: Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling. This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB; also known as CRTC). Our findings indicate that striatal miR-212 signalling has a key role in determining vulnerability to cocaine addiction, reveal new molecular regulators that control the complex actions of cocaine in brain reward circuitries and provide an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs.
TL;DR: In this paper, the authors used data from two case studies to highlight the importance of context in the life of a gamer and demonstrates that excessive gaming does not necessarily mean that a person is addicted.
Abstract: Research into online gaming addiction is a relatively new area of psychological study. Furthermore, there are studies that have claimed that online gaming addiction may be addictive because of self-report accounts of very excessive use of up to 80 h a week. This study uses data from two case studies to highlight the role of context in distinguishing excessive gaming from addictive gaming. Both of the gamers in this study claimed to be playing for up to 14 h a day yet and although they were behaviorally identical in terms of their game playing, they were very different in terms of psychological motivation and the meaning and experience of gaming within their lives. It is argued that one of the players appears to be genuinely addicted to online gaming but that the other player is not based on context and consequences. The two cases outlined highlight the importance of context in the life of a gamer and demonstrates that excessive gaming does not necessarily mean that a person is addicted. It is argued that online gaming addiction should be characterized by the extent to which excessive gaming impacts negatively on other areas of the gamers’ lives rather than the amount of time spent playing. It is also concluded that an activity cannot be described as an addiction if there are few (or no) negative consequences in the player’s life even if the gamer is playing 14 h a day.
TL;DR: κ receptor agonists antagonize the reinforcing/rewarding effects of drugs possibly through punishing/aversive-like effects and reinstate drug seeking through stress- like effects and evidence suggests that abused drugs activate the κ opioid system, which may play a key role in motivational aspects of dependence.
Abstract: Background
Initial hypotheses regarding the role of the κ opioid system in drug addiction suggested that κ receptor stimulation had anti-addictive effects. However, recent research suggests that κ receptor antagonists may reverse motivational aspects of dependence. In the present review, we revisit the studies that measured the effects of κ receptor ligands on the reinforcing and rewarding effects of drugs and postulate underlying neurobiological mechanisms for these effects to elaborate a more complex view of the role of κ receptor ligands in drug addiction.
TL;DR: It is suggested that neuronal functions associated with dopaminergic signaling, such as the attribution of salience to reward-predicting stimuli and the computation of prediction errors, are indeed altered in schizophrenia patients and that this impairment appears to contribute to delusion formation.
Abstract: A dysregulation of the mesolimbic dopamine system in schizophrenia patients may lead to aberrant attribution of incentive salience and contribute to the emergence of psychopathological symptoms like delusions. The dopaminergic signal has been conceptualized to represent a prediction error that indicates the difference between received and predicted reward. The incentive salience hypothesis states that dopamine mediates the attribution of "incentive salience" to conditioned cues that predict reward. This hypothesis was initially applied in the context of drug addiction and then transferred to schizophrenic psychosis. It was hypothesized that increased firing (chaotic or stress associated) of dopaminergic neurons in the striatum of schizophrenia patients attributes incentive salience to otherwise irrelevant stimuli. Here, we review recent neuroimaging studies directly addressing this hypothesis. They suggest that neuronal functions associated with dopaminergic signaling, such as the attribution of salience to reward-predicting stimuli and the computation of prediction errors, are indeed altered in schizophrenia patients and that this impairment appears to contribute to delusion formation.
TL;DR: There was a close relationship between IA tendencies and depression, such that IA respondents were more depressed; there were also significant differences between the sexes, with men showing more addictive tendencies than women.
Abstract: Background: There is a growing awareness of a psychiatric construct that needs to be better defined and understood: Internet addiction (IA). Recently there has been much public conc
TL;DR: Using a rat model of addiction, it is found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake.
Abstract: Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.
TL;DR: It is shown that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABAA (γ-aminobutyric acid type A) receptors in nearby interneurons, and that subunit-selective benzodiazines sparing α1 may be devoid of addiction liability.
Abstract: Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha1-containing GABA(A) receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of alpha1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction liability.
TL;DR: For example, this paper found that high-responder rats (bHRs) were more impulsive on a measure of impulsive action, i.e., they had difficulty withholding an action to receive a reward, indicative of behavioral disinhibition.
TL;DR: A convergence of evidence suggests that women with substance use disorders are more likely than men to face multiple barriers affecting access and entry to substance abuse treatment.
Abstract: Substance use was considered to be primarily a male problem, and many substance abuse studies are conducted with a predominance of male participants. However, recent substance abuse research indicates significant gender differences in the substance-related epidemiology, social factors and characteristics, biological responses, progressions to dependence, medical consequences, co-occurring psychiatric disorders, and barriers to treatment entry, retention, and completion. The epidemiology of women's drug use presents challenges separate from those raised by men's drug use. A convergence of evidence suggests that women with substance use disorders are more likely than men to face multiple barriers affecting access and entry to substance abuse treatment. Gender-specific medical problems as a result of the interplay of gender-specific drug use patterns and sex-related risk behaviors create an environment in which women are more vulnerable than men to human immunodeficiency virus. Individual characteristics and treatment approaches can differentially affect outcomes by gender. All of these differences have important clinical, treatment, and research implications.
TL;DR: An up-to-date review of the literature on opioid dependence treatment, with a focus on evidence for inclusion of psychosocial approaches in treatment regimens, either as stand-alone or in conjunction with psychopharmacological options.
TL;DR: The potential mechanisms by which ethanol impacts brain development and lead to brain impairments and cognitive and behavioral dysfunctions are reviewed as well as the neurobiological and neurochemical processes underlying the adolescent-specific vulnerability to drug addiction are reviewed.
TL;DR: The concept of self-regulation, combined with the concept of modularity of cognitive function, may aid in the understanding of the neural basis of individual differences in the vulnerability to drugs and the transition to addiction.
TL;DR: This review explores the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggests how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use.
TL;DR: Evidence for the existence of dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression is discussed.
Abstract: Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a potential therapeutic target to improve mood and socio-affiliative behaviors in patients with profound social deficits and/or drug addiction.
TL;DR: Observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state.
TL;DR: It is demonstrated that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value and its corresponding neural representation in the striatum, which leads to a state of excessive discounting of temporally distant, relative to sooner, rewards.
Abstract: Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.
TL;DR: Multimodal school-based group CBT is effective for adolescents with Internet addiction, particularly in improving emotional state and regulation ability, behavioural and self-management style.
Abstract: Objective: The aim of the present study was to evaluate the therapeutic effectiveness of group cognitive behavioural therapy (CBT) for Internet addiction in adolescents.Method: A total of 56 patients, who met Beard's diagnostic criteria for Internet addiction, aged 12–17 years, were divided randomly into an active treatment group (n = 32) and a clinical control group (n = 24). Participants in the active treatment group were treated with an eight-session multimodal school-based group CBT while participants in the clinical control group received no intervention. Internet use, time management, emotional, cognitive and behavioural measures were assessed for both groups at baseline, immediately after the intervention and at 6 month follow up by investigators blind to the participants’ group status.Results: Internet use decreased in both groups while only the multimodal school-based group CBT evinced improved time management skills and better emotional, cognitive and behavioural symptoms.Conclusions: Multimodal...
TL;DR: This work reports the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence.