Addiction: A Disease of Learning and Memory

Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 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.

13 Reads
    • "Drug addiction can be characterized as a disorder of maladaptive learning and memory (Everitt, Dickinson, & Robbins, 2001). Addictive drugs have the ability to hijack the natural reward system and influence the strength of memories that predict reward (Everitt et al., 2001; Hyman, 2005; Hyman, Malenka, & Nestler, 2006; Torregrossa, Corlett, & Taylor, 2011). These memories can be linked to external cues in the environment that have previously been accompanied by drug use (Crombag & Shaham, 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decade, a growing body of research has sought to investigate how the pharmacological disruption of memory reconsolidation can degrade or erase memories. Much of this research has focused specifically on disrupting memories that are considered bad or maladaptive for the ultimate purpose of translation to a human population. While most of the research was pioneered in fear memory, recent studies have focused on degrading drug-cued memories in the context of addiction. Essentially, this research seeks to disrupt cues as predictors of reward or drug availability. A core component of this reconsolidation process is glutamate signaling. An overall review of the literature suggests that disruption of glutamate signaling under reconsolidation parameters is sufficient to erase drug-related memories. This review will focus on specific studies that examine the glutamatergic mechanisms of reconsolidation disruption in the context of drug addiction.
    Journal of Applied Biobehavioral Research 09/2015; 20(3). DOI:10.1111/jabr.12031
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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 · 3.66 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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
Show more