Article

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.

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    • "Phasic bursts, in turn, influence learning and motivation in manner distinct from tonic DA activity [57,58]. Additionally, rewarding and aversive events trigger changes in behavioral and cognitive processing aimed to engage in fitted decision-making, (see [4,51]). DA neurons are proposed to transmit their signals to distinct brain structures in order to support distinct neural systems for motivated cognition and behaviors. "
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    ABSTRACT: In this review we describe how highly addictive psychostimulants such as cocaine and methamphetamine actions might underlie hypoexcitabilty in frontal cortical areas observed in clinical and preclinical models of psychostimulant abuse. We discuss new mechanisms that describe how increments on synaptic dopamine release are linked to reduce calcium influx in both pre and postsynaptic compartments on medial PFC networks, therefore modulating synaptic integration and information. Sustained DA neuromodulation by addictive psychostimulants can “lock” frontal cortical networks in deficient states. On the other hand, other psychostimulants such as modafinil and methylphenidate are considered pharmacological neuroenhancement agents that are popular among healthy people seeking neuroenhancement. More clinical and preclinical research is needed to further clarify mechanisms of actions and physiological effects of cognitive enhancers which show an opposite pattern compared to chronic effect of addictive psychostimulants: they appear to increase cortical excitability. In conclusion, studies summarized here suggest that there is frontal cortex hypoactivity and deficient inhibitory control in drug-addicted individuals. Thus, additional research on physiological effects of cognitive enhancers like modafinil and methylphenidate seems necessary in order to expand current knowledge on mechanisms behind their therapeutic role in the treatment of addiction and other neuropsychiatric disorders.
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    • "Research, using diverse methods, has converged on the point that the dopamine (DA) system is fundamentally important to reward related behaviors (Berridge and Robinson, 1998; Hyman, 2005; Palmiter, 2008). It has been well established that drugs producing rewarding effects are dependent on their ability to elevate extracellular DA levels in the mesolimbic DA system (Koob and Volkow, 2010). "
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    ABSTRACT: It is well known that dopamine (DA) is critical for reward, but the precise role of DA in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of DA-deficient rhesus monkeys in a morphine-induced conditioned place preference (CPP) paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference that was equivalent to control monkeys. However, these monkeys could not maintain the preference as well as controls when they retained severe Parkinsonian symptoms. On the other hand, monkeys initially in a severe Parkinsonian state developed a preference for morphine, but this preference was weaker than that of the controls. Histological results showed that the loss of dopaminergic neurons in monkeys that had severe Parkinsonian symptoms was about 80% in comparison to the control monkeys. All these data suggest that a severely impaired DA system alters rewarding-seeking behavior in non-human primates.
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    • "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). "
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