Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through 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.

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

Many organisms, especially humans, are characterized by their capacity for intentional, goal-directed actions. However, similar behaviours often proceed automatically, as habitual responses to antecedent stimuli. How are goal-directed actions transformed into habitual responses? Recent work combining modern behavioural assays and neurobiological analysis of the basal ganglia has begun to yield insights into the neural basis of habit formation.

The role of the basal ganglia in habit formation

http://egret.psychol.cam.ac.uk/publications/2002/9_Cardinal_2002_NBBR_26_321_Emotion_and_motivation_amygdala_VS_PFC_MANUSCRIPT.pdf

Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex

http://egret.psychol.cam.ac.uk/publications/2004/19_Dalley_2004_NBBR_28_771_Prefrontal_exec_function_in_rodents.pdf

Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates

Habits are controlled by antecedent stimuli rather than by goal expectancy. Interval schedules of feedback have been shown to generate habits, as revealed by the insensitivity of behaviour acquired under this schedule to outcome devaluation treatments. Two experiments were conducted to assess the role of the dorsolateral striatum in habit learning. In Experiment 1, sham operated controls and rats with dorsolateral striatum lesions were trained to press a lever for sucrose under interval schedules. After training, the sucrose was devalued by inducing taste aversion to it using lithium chloride, whereas saline injections were given to the controls. Only rats given the devaluation treatment reduced their consumption of sucrose and this reduction was similar in both the sham and the lesioned groups. All rats were then returned to the instrumental chamber for an extinction test, in which the lever was extended but no sucrose was delivered. In contrast to sham operated controls, rats with dorsolateral striatum lesions refrained from pressing the lever if the outcome was devalued. To assess the specificity of the role of dorsolateral striatum in this effect a second experiment was conducted in which a group with lesions of dorsomedial striatum was added. In relation now to both the sham and the dorsomedial lesioned groups, only rats with lesions of dorsolateral striatum significantly reduced responding after outcome devaluation. In conclusion, this study provides direct evidence that the dorsolateral striatum is necessary for habit formation. Furthermore, it suggests that, when the habit system is disrupted, control over instrumental performance reverts to the system controlling the performance of goal-directed instrumental actions.

Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning.

Two experiments investigated performance of instrumental lever pressing by rats following post-conditioning devaluation of the sucrose reinforcer produced by establishing an aversion to it. In Experiment I rats responded less in an extinction test after being averted from the sucrose following training on a ratio schedule, but not following an equivalent amount of training on an interval schedule. This was true even though the devalued sucrose would not act as an effective reinforcer on either the ratio or interval schedule. Experiment II provided a further investigation of the insensitivity of interval responding to reinforcer devaluation by comparing test performance under simple extinction with responding when the devalued reinforcer was presented on either a response-contingent or non-contingent schedule during the test. Once again simple extinction performance was unaffected by prior reinforcer devaluation. Furthermore, neither non-contingent nor contingent presentations of the devalued reinforcer si...

The effect of the instrumental training contingency on susceptibility to reinforcer devaluation

The development of suppression in rats to a target conditioned stimulus (CS) was compared in trace and serial conditioning procedures. The interval between the end of the target CS and the shock unconditioned stimulus (US) was filled by a second CS in the serial, but not the trace, procedure. In five experiments the serial procedure produced superior conditioning. This potentiation effect, however, depended critically upon the level of conditioning to the stimulus interpolated between the target CS and the US. When conditioning to the interpolated CS was either reduced by giving independent nonreinforced trials with this CS alone or enhanced by independent reinforced trials, the potentiation effect was abolished. In addition, the insertion of a trace interval between the target and interpolated CSs reduced the effect. However, the magnitude of conditioning to the target CS was unaffected by post-conditioning changes in the conditioned strength of the interpolated CS. These findings are discussed in terms ...

The potentiation effect during serial conditioning.

Four experiments investigated the processes by which a motivationally-induced change in the value of the training reinforcer affects instrumental performance. Initially, thirsty rats were trained to lever press for either a sodium or non-sodium solution. In Experiment I sodium-trained rats responded faster in extinction following the induction of a sodium appetite, but not following either food or water deprivation. Thus, enhanced extinction performance depends upon the relevance of the training reinforcer to the test drive state. The remaining experiments examined the role of the instrumental contingency. Animals received response-contingent presentations of one solution alternated either within (Experiments II and III) or between sessions (Experiment IV) with non-contingent presentations of another solution. Neither procedure yielded convincing evidence that contingent sodium presentations generated more responding in extinction under a sodium appetite than did non-contingent sodium presentations. On th...

Irrelevant incentive learning during instrumental conditioning: The role of the drive-reinforcer and response-reinforcer relationships

In each of three experiments two groups of rats received inhibitory conditioning to one stimulus. Prior to a test phase of excitatory conditioning to this stimulus, one group was repeatedly exposed...

Loss of associability by a conditioned inhibitor.

Two experiments investigated the effect of a motivationally-induced change in the value of the training reinforcer on instrumental performance. Initially, thirsty rats were trained to lever press for either a sodium or a potassium solution. Responding in an extinction test was then measured following the induction of sodium appetite. In Experiment I sodium-trained rats responded faster in a test given one day following the end of instrumental training. Furthermore, the relative size of this irrelevant incentive effect did not depend upon whether a ratio or interval schedule was employed during training. Delaying the test for eight days following the end of training abolished the difference between the test performance of sodium- and potassium-trained animals. Experiment II provided a further study of the effect of the training schedule when the introduction of the sodium reinforcer was delayed until responding was well established. Again the relative size of the difference between the performance of sodiu...

D. J. Nicholas

Papers

The effect of the instrumental training contingency on susceptibility to reinforcer devaluation

The potentiation effect during serial conditioning.

Irrelevant incentive learning during instrumental conditioning: The role of the drive-reinforcer and response-reinforcer relationships

Loss of associability by a conditioned inhibitor.

Irrelevant incentive learning during training on ratio and interval schedules