Glutamate transmission in addiction

Kalivas, Peter W.; LaLumiere, Ryan T.; Knackstedt, Lori A.; Shen, Haowei

doi:10.1016/j.neuropharm.2008.07.011

Cited by 347 publications

(280 citation statements)

References 76 publications

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“…Results from the present study are consistent with literature implicating plastic changes in multiple nodes of the brain reward network in the development, maintenance, and/ or resumption of substance use (Baler and Volkow, 2006;Kalivas and O'Brien, 2008;Kalivas et al, 2009;McFarland et al, 2003;Sher et al, 2005;Volkow and Fowler, 2000;Volkow et al, 2001Volkow et al, , 2004. The overall pattern of results from the present study parallels the morphological fi ndings by Wrase and colleagues (2008), who observed lower amygdala volume in alcohol-dependent individuals who relapsed after treatment, compared with those who remained abstinent and relative to controls (the amygdala is a crucial component of the brain reward system involved in the determination of the emotional valence of a stimulus; Kalivas and Volkow, 2005).…”

Section: Discussionsupporting

confidence: 91%

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

Durazzo¹,

Pathak²,

Gaździński³

et al. 2010

J. Stud. Alcohol Drugs

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ABSTRACT. Objective:This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. Method: Fiftyone treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, cholinecontaining compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classifi ed as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. Results: Resumers demonstrated signifi cantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. Conclusions: The signifi cantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers. A LCOHOL-USE DISORDERS (AUDs; i.e., alcohol dependence and abuse) are characterized by a chronically relapsing/remitting course over the lifetime (Dawson et al., 2007;Jin et al., 1998;Miller et al., 2001;Zywiak et al., 2006). The resumption of hazardous levels of alcohol consumption after treatment is common (Donovan, 1996;Maisto and Connors, 2006;Miller et al., 2001;Monahan and Finney, 1996), and appears to be mediated by a complex interplay among genetic, neurobiological, neurocognitive, psychological/psychiatric, and sociodemographic factors (Adinoff et al., 2005;Baler and Volkow, 2006;Bottlender and Soyka, 2005;Bradizza et al., 2006;Glenn and Parsons, 1991;Goodman, 2008;Heinz et al., 2003;Jin et al., 1998;Koob, 2003;Moos and Moos, 2006;Parsons et al., 1990;Sher et al., 2005;Weiss and Porrino, 2002;Zywiak et al., 2006). A considerable amount of research has inve...

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Section: Discussionsupporting

confidence: 91%

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

Durazzo¹,

Pathak²,

Gaździński³

et al. 2010

J. Stud. Alcohol Drugs

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“…47,48 More recently, data are emerging suggesting a role of oxidative stress in the pathophysiology of addiction to drugs of abuse. 32,[49][50][51] Research has explored the modulation of glutamatergic pathways by NAC in preclinical models.…”

Section: Addictionmentioning

confidence: 99%

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Dean

Giorlando

Berk

2011

J Psychiatry Neurosci

421

314

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There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.

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“…Drugs of abuse such as amphetamine and cocaine usurp this basic function, essentially hijacking the circuitry via induction of maladaptive plasticity (Kauer and Malenka 2007;Kalivas et al 2009;Chen et al 2010;Russo et al 2010; Van den Oever et al 2010;Badiani et al 2011;Luscher and Malenka 2011;Sulzer 2011). As mentioned above, the dopaminergic mesolimbic pathway and its associated neuroanatomical structures are heavily implicated in drug-induced neuropathology ( Fig.…”

Section: Basic Neuroanatomy Of Reward Circuitrymentioning

confidence: 99%

Mechanisms of Psychostimulant-Induced Structural Plasticity

Golden

Russo

2012

Cold Spring Harbor Perspectives in Medicine

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Psychostimulants robustly induce alterations in neuronal structural plasticity throughout brain reward circuits. However, despite our extensive understanding of how these circuits modulate motivated behavior, it is still unclear whether structural plasticity within these regions drives pathological behavioral responses in addiction. Although these structural changes have been subjected to an exhaustive phenomenological characterization, we still have a limited understanding of the molecular mechanisms regulating their induction and the functional relevance of such changes in mediating addiction-like behavior. Here we have highlighted the known molecular pathways and intracellular signaling cascades that regulate psychostimulant-induced changes in neuronal morphology and synaptic restructuring, and we discuss them in the larger context of addiction behavior.

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Glutamate transmission in addiction

Cited by 347 publications

References 76 publications

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Mechanisms of Psychostimulant-Induced Structural Plasticity

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