Addiction: A Disease of Learning and Memory

Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
American Journal of Psychiatry (Impact Factor: 13.56). 09/2005; 162(8):1414-22. DOI: 10.1176/appi.ajp.162.8.1414
Source: PubMed

ABSTRACT If neurobiology is ultimately to contribute to the development of successful treatments for drug addiction, researchers must discover the molecular mechanisms by which drug-seeking behaviors are consolidated into compulsive use, the mechanisms that underlie the long persistence of relapse risk, and the mechanisms by which drug-associated cues come to control behavior. Evidence at the molecular, cellular, systems, behavioral, and computational levels of analysis is converging to suggest the view that addiction represents a pathological usurpation of the neural mechanisms of learning and memory that under normal circumstances serve to shape survival behaviors related to the pursuit of rewards and the cues that predict them. The author summarizes the converging evidence in this area and highlights key questions that remain.

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    • "Forexample,Simonyietal.(2010)reviewednumerousani- malstudieswhichemployedmGluR5receptorantagonistsin knockoutmicetodeterminetheroleofmGluR5inlearning andmemory.Inhibitorylearning,suchaspassiveavoidance learning,isawell-establishedtaskinanimalmodelsthatisused tostudyhippocampallearningprocesses,andhasbeenshown innumerousstudiestobedependentonthemGluR5receptor (Simonyietal.,2010).Forinstance,researchdemonstrated hyperexpressionofmGluR5proteininCA3duringshort- andCA1long-termpotentiationinrats(Riedeletal.,2000). Hyman(2005)presentedabiologicalmodelofaddictionthat incorporatesabnormalneuralprocessesoflearningandmemory formingthebasicelementsofaddiction.Theauthorsproposed thatlong-termpotentiation,whichincludes,alterationsinthe availabilityofglutamatereceptors,andregulationofgeneexpres- sionaspotentiallyimportantmechanismsforthedrug-induced alterationsfoundintheabnormalcircuitsassociatedwithdrug addiction.Finally,thestudiesonmGluR5andsleephomeostasis (Heftietal.,2013;Ahnaouetal.,2015)suggestanimportant roleofmGluR5inRDoC'sarousalandmodulatorysystems domain. "
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    ABSTRACT: In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.
    Frontiers in Neuroscience 03/2015; 9:86. DOI:10.3389/fnins.2015.00086 · 3.70 Impact Factor
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    • "Addicted individuals display a behavioral repertoire restricted to repeated cycles of drug seeking, consumption and recovery from drug use despite often severe negative consequences (Hyman, 2005). Drug addiction is the endpoint of a series of transitions from initial, hedonic drug use to habitual and ultimately compulsive drug use, which coincides with long-lasting adaptations in neural circuits (Robinson and Berridge, 1993; Kalivas and Volkow, 2005). "
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    ABSTRACT: The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.
    Frontiers in Systems Neuroscience 12/2014; 8:230. DOI:10.3389/fnsys.2014.00230
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    • "But it may also create problems. For example, many drugs of abuse produce potent neural reward signals (Dayan, 2009; Hyman, 2005; Robinson & Berridge, 2001). Involuntary attentional capture by stimuli associated with these drug rewards (such as drug paraphernalia, or people and locations associated with drug supply) is known to predict relapse in recovering addicts (Cox, Hogan, Kristian, & Race, 2002; Marissen et al., 2006; Waters et al., 2003). "
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    ABSTRACT: Attention provides the gateway to cognition, by selecting certain stimuli for further analysis. Recent research demonstrates that whether a stimulus captures attention is not determined solely by its physical properties, but is malleable, being influenced by our previous experience of rewards obtained by attending to that stimulus. Here we show that this influence of reward learning on attention extends to task-irrelevant stimuli. In a visual search task, certain stimuli signaled the magnitude of available reward, but reward delivery was not contingent on responding to those stimuli. Indeed, any attentional capture by these critical distractor stimuli led to a reduction in the reward obtained. Nevertheless, distractors signaling large reward produced greater attentional and oculomotor capture than those signaling small reward. This counterproductive capture by task-irrelevant stimuli is important because it demonstrates how external reward structures can produce patterns of behavior that conflict with task demands, and similar processes may underlie problematic behavior directed toward real-world rewards. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Journal of Experimental Psychology General 11/2014; 144(1). DOI:10.1037/xge0000037 · 5.50 Impact Factor
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