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      The transition to compulsion in addiction

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          Abstract

          <p class="first" id="P1">Compulsion is a cardinal symptom of drug addiction (severe substance use disorder). However, compulsion is observed in only a small proportion of individuals who repeatedly seek and use addictive substances. Here, we integrate accounts of the neuropharmacological mechanisms that underlie the transition to compulsion with overarching learning theories, to outline how compulsion develops in addiction. Importantly, we emphasize the conceptual distinctions between compulsive drug-seeking behaviour and compulsive drug-taking behaviour (that is, use). In the latter, an individual cannot stop using a drug despite major negative consequences, possibly reflecting an imbalance in frontostriatal circuits that encode reward and aversion. By contrast, an individual may compulsively seek drugs (that is, persist in seeking drugs despite the negative consequences of doing so) when the neural systems that underlie habitual behaviour dominate goal-directed behavioural systems, and when executive control over this maladaptive behaviour is diminished. This distinction between different aspects of addiction may help to identify its neural substrates and new treatment strategies. </p>

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          Most cited references153

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          Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action.

          Recent behavioral studies in both humans and rodents have found evidence that performance in decision-making tasks depends on two different learning processes; one encoding the relationship between actions and their consequences and a second involving the formation of stimulus-response associations. These learning processes are thought to govern goal-directed and habitual actions, respectively, and have been found to depend on homologous corticostriatal networks in these species. Thus, recent research using comparable behavioral tasks in both humans and rats has implicated homologous regions of cortex (medial prefrontal cortex/medial orbital cortex in humans and prelimbic cortex in rats) and of dorsal striatum (anterior caudate in humans and dorsomedial striatum in rats) in goal-directed action and in the control of habitual actions (posterior lateral putamen in humans and dorsolateral striatum in rats). These learning processes have been argued to be antagonistic or competing because their control over performance appears to be all or none. Nevertheless, evidence has started to accumulate suggesting that they may at times compete and at others cooperate in the selection and subsequent evaluation of actions necessary for normal choice performance. It appears likely that cooperation or competition between these sources of action control depends not only on local interactions in dorsal striatum but also on the cortico-basal ganglia network within which the striatum is embedded and that mediates the integration of learning with basic motivational and emotional processes. The neural basis of the integration of learning and motivation in choice and decision-making is still controversial and we review some recent hypotheses relating to this issue.
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            Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On.

            A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.
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              Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

              Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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                Author and article information

                Journal
                Nature Reviews Neuroscience
                Nat Rev Neurosci
                Springer Science and Business Media LLC
                1471-003X
                1471-0048
                March 30 2020
                Article
                10.1038/s41583-020-0289-z
                7610550
                32231315
                13769073-7496-4ffd-acc7-a960d74f7839
                © 2020

                http://www.springer.com/tdm

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