Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

REVIEWNEUROBIOLOGY OF ADDICTION.com/natureneuroscienceNeural systems of reinforcement for

drug addiction: from actions to habits to

compulsionhttp://www.natureBarry J Everitt & Trevor W RobbinsDrug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug usewhen a drug is voluntarily

taken because it has reinforcing, often hedonic, effectsthrough loss of control over this behavior, such that it becomes

habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian

and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive

drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking

behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation.

These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by

chronic self-administration of drugs.The nucleus accumbens is well known to mediate the reinforcing effects

of drugs, but more recent research emphasizes the role of the striatum as a

whole, including the shell and core components of the nucleus accumbens,

in the processes leading first to drug abuse and then to addiction. This view

has been stimulated by progress in understanding the dopamine-dependent, serial communication between the various domains of the striatum

via a cascading loop interconnectivity1, and by an improved understanding of associative learning mechanisms that conceive of behavioral

output as an interaction between pavlovian and instrumental learning

processes2,3. In particular, the description of two processes that seem to

function partly in parallel, but with the second eventually dominating

behavioral output, has led to the concepts of action-outcome and stimulus-response (habit) learning. Here we elaborate the hypothesis that these

behavioral processes can be mapped onto the parallel and serial, dynamic

functioning of corticostriatal circuitry (Fig. 1) to mediate the switches4,5

between drug reinforcement, drug abuse and drug addiction.Reinforcement, conditioning and the nucleus accumbensThe reinforcing effects of addictive drugs are multidimensional

(Box 1). Drugs act as instrumental reinforcersthat is, they increase

the likelihood of responses that produce them, resulting in drug

self- administration or drug taking (defined in Box 2). Environmental

stimuli that are closely associated in time and space with the effects

of...