Abstract
This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus–response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse.
Highlights
Many people take drugs that are addictive and do so for different reasons, in different ways and in different contexts, for example the social drinking of alcohol, which is acceptable in some but not all societies, or the more solitary intravenous use of drugs such as heroin
We have recently presented data and reviewed the evidence (Belin et al, 2013; Everitt & Robbins, 2013) suggesting that these interactions and transitions between ventral and dorsal striatal domains depend in a significant way upon the recurrent circuitry that, via projections to midbrain DA neurons, allows ventral striatal processing to influence DA-dependent processing in the dorsal striatum (Haber et al, 2000) – links the NAcb shell to the core, to the DMS and the DLS via connections with progressively more lateral midbrain DA neurons – from medial ventral tegmental area to lateral substantia nigra (Fig. 2)
In a closely related in vivo neurochemical study, it was further shown in rats self-administering cocaine that late-developing drug conditioned stimulus (CS)-evoked DA transients in the anterior dosolateral striatum (aDLS) were completely prevented by an NAcb core lesion, providing direct evidence in a behavioural setting that DA release in the aDLS depended on antecedent processing in the NAcb core (Willuhn et al, 2012)
Summary
Many people take drugs that are addictive and do so for different reasons, in different ways and in different contexts, for example the social drinking of alcohol, which is acceptable in some but not all societies, or the more solitary intravenous use of drugs such as heroin. The basolateral amygdala (BLA) is a major source of afferents to the ventral striatum, especially to the nucleus accumbens core, and to the shell region (Wright et al, 1996) This system provides the basis for interactions between stimulus–reward associative processing in the amygdala and the primary site mediating the reinforcing effects of addictive drugs, the ventral striatum, thereby underlying both pavlovian and instrumental appetitive behaviours – much as Mogenson et al (1984) had predicted when describing this system as a ‘limbic-motor interface’ (Fig. 2). These data argue for the parallel involvement of the BLA, NAcb core, pDMS and OFC in the acquisition and performance of goaldirected cocaine seeking maintained over delays to drug reward and sustained by drug-associated conditioned reinforcement (Fig. 2)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
