Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: An event-related fMRI study

Li, Qiang; Wang, Yarong; Zhang, Yi; Li, Wei; Yang, Weichuan; Zhu, Jiang; Wu, Ning; Chang, Haifeng; Zheng, Ying; Qin, Wei; Zhao, Liyan; Yuan, Kai; Liu, Jixin; Wang, Wei; Tian, Jie

doi:10.1016/j.brainres.2012.06.024

Cited by 115 publications

(84 citation statements)

References 45 publications

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“…These studies have generally demonstrated that relative to controls, cocaine-addicted individuals exhibit enhanced activation in prefrontal regions following exposure to drug-associated stimuli, particularly in cingulate cortex (Kilts et al, 2004; Kuhn and Gallinat, 2011; Marhe et al, 2013; Wexler et al, 2001), left lateral OFC and right dorsolateral PFC (Bonson et al, 2002). Activation of prefrontal regions following exposure to drug cues has also been reported in nicotine (Brody et al, 2002; Brody et al, 2007; Kober et al, 2010b; Yalachkov et al, 2009), alcohol (Grusser et al, 2004; Heinz et al, 2007) and heroin (Li et al, 2012; Li et al, 2013; Li et al, 2014; Xiao et al, 2006) addicted individuals. Importantly, measures of PFC activity following cue exposure appear to have some clinical relevance (Goldstein and Volkow, 2011).…”

Section: Pfc In Drug Abuse and Addiction In Humansmentioning

confidence: 84%

Differential roles of medial prefrontal subregions in the regulation of drug seeking

et al. 2015

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The prefrontal cortex plays an important role in shaping cognition and behavior. Many studies have shown that medial prefrontal cortex (mPFC) plays a key role in seeking, extinction, and reinstatement of cocaine seeking in rodent models of relapse. Subregions of mPFC appear to play distinct roles in these behaviors, such that the prelimbic cortex (PL) is proposed to drive cocaine seeking and the infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction. This dichotomy of mPFC function may be a general attribute, as similar dorsal-ventral distinctions exist for expression vs. extinction of fear conditioning. However, other results indicate that the role of mPFC neurons in reward processing is more complex than a simple PL-seek vs. IL-extinguish dichotomy. Both PL and IL have been shown to drive and inhibit drug seeking (and other types of behaviors) depending on a range of factors including the behavioral context, the drug-history of the animal, and the type of drug investigated. This heterogeneity of findings may reflect multiple subcircuits within each of these PFC areas supporting unique functions. It may also reflect the fact that the mPFC plays a multifaceted role in shaping cognition and behavior, including those overlapping with cocaine seeking and extinction. Here we discuss research leading to the hypothesis that dorsal and ventral mPFC differentially control drug seeking and extinction. We also present recent results calling the absolute nature of a PL vs. IL dichotomy into question. Finally, we consider alternate functions for mPFC that correspond less to response execution and inhibition and instead incorporate the complex cognitive behavior for which the mPFC is broadly appreciated.

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Section: Pfc In Drug Abuse and Addiction In Humansmentioning

confidence: 84%

Differential roles of medial prefrontal subregions in the regulation of drug seeking

et al. 2015

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“…Indeed, upon additional experimentation eliminating drug-predictive cues, we demonstrated that the Her-KLH vaccine can effectively eliminate the motivational valence of heroin psychoactivity, even in the original drug context. Numerous studies have demonstrated that heroin cues and contexts can produce reward activation in the brains of opiate addicts (36,37) and stimulate dopamine release, which plays a role in the cognitive processing of drug associations (31,38). Clearly, behavioral therapy, in conjunction with any vaccine treatment, will be needed to overcome such associative factors and further abate drug-seeking behavior.…”

Section: Discussionmentioning

confidence: 99%

Dynamic vaccine blocks relapse to compulsive intake of heroin

Schlosburg

Vendruscolo

Bremer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine. We recently developed a "dynamic" vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin's metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin selfadministration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brainpermeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin's psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.immunotherapy | antinociception | progressive ratio

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“…Basal heroin craving was assessed using a 0-10 visual analogue scale [20][21][22] asking, "To what extent do you feel the urge to use heroin?" (0 indicated the least and 10 indicated the strongest craving).…”

Section: Evaluation Measuresmentioning

confidence: 99%

Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men

Liu

Wang

et al. 2018

jpn

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IntroductionCognitive dysfunction is a key component of addictive disorders. With heroin addiction, specific deficits in salience attribution and inhibitory control emerge during long-term drug abuse and promote heroin relapse during withdrawal.1 Although most heroin-dependent individuals are willing to quit, available interventions for heroin addiction have shown only limited efficacy so far. Methadone maintenance treatment programs (MMTPs) are a common treatment approach thought to be effective for heroin addiction; however, the heroin-dependent patients in MMTPs are at high risk for relapse, with about 70% of individuals relapsing once they leave such a program.2 Despite the high relapse rate, few neuroimaging studies so far have addressed the neural predictors of risk for heroin relapse. Studies using task-related functional MRI (fMRI) have shown some usefulness in identifying relapse predictors 3-5 or quitting predictors. 6,7 For example, a previous study by our group showed that drugrelated cues induced activity of the nucleus accumbens/ subcallosal cortex and that the cerebellum was associated with subsequent relapse in heroin-dependent individuals. 3Brain activity associated with error processing was shown to predict relapse in cocaine-dependent patients.4 Disrupted ventromedial prefrontal function was shown to be associated with relapse in alcohol-dependent patients.5 Greater response of the medial prefrontal cortex and precuneus to self-related tailored smoking-cessation messages was shown to be associated with quitting. 6 And pretreatment medial prefrontal cortical response to heroin-related cues was shown to be associated with greater adherence to injectable extended-release naltrexone.7 However, more effective imaging markers that We conducted a prospective resting-state functional MRI study comparing the functional connectivity strength among healthy controls and heroin-dependent men who had either relapsed or were in early remission. Men were considered to be either relapsed or in early remission based on urine drug screens during a 3-month follow-up period. We also examined how the coupling of large-scale networks correlated with relapse behaviour among heroin-dependent men. Results: We included 20 controls and 50 heroin-dependent men (26 relapsed and 24 early remission) in our analyses. The relapsed men showed greater connectivity than the early remission and control groups between the dorsal anterior cingulate cortex (key node of the SN) and the dorsomedial prefrontal cortex (included in the DMN). The relapsed men and controls showed lower connectivity than the early remission group between the left dorsolateral prefrontal cortex (key node of the left ECN) and the dorsomedial prefrontal cortex. The percentage of positive urine drug screens positively correlated with the coupling between the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex, but negatively correlated with the coupling between the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Limitations:...

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Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: An event-related fMRI study

Cited by 115 publications

References 45 publications

Differential roles of medial prefrontal subregions in the regulation of drug seeking

Differential roles of medial prefrontal subregions in the regulation of drug seeking

Dynamic vaccine blocks relapse to compulsive intake of heroin

Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men

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