Nucleus accumbens shell and core dopamine: differential role in behavior and addiction.

Drug addiction can be conceptualized as a disturbance of behavior motivated by drug-conditioned incentives. This abnormality has been explained by Incentive-Sensitization and Allostatic-Counteradaptive theories as the result of non-associative mechanisms acting at the stage of the expression of incentive motivation and responding for drug reinforcement. Each one of these theories, however, does not account per se for two basic properties of the motivational disturbance of drug addiction: (1). focussing on drug- at the expenses of non-drug-incentives; (2). virtual irreversibility. To account for the above aspects we have proposed an associative learning hypothesis. According to this hypothesis the basic disturbance of drug addiction takes place at the stage of acquisition of motivation and in particular of Pavlovian incentive learning. Drugs share with non-drug rewards the property of stimulating dopamine (DA) transmission in the nucleus accumbens shell but this effect does not undergo habituation upon repeated drug exposure, as instead is the case of non-drug rewards. Repetitive, non-decremental stimulation of DA transmission by drugs in the nucleus accumbens septi (NAc) shell abnormally strengthens stimulus-drug associations. Thus, stimuli contingent upon drug reward acquire powerful incentive properties after a relatively limited number of predictive associations with the drug and become particularly resistant to extinction. Non-contingent occurrence of drug-conditioned incentive cues or contexts strongly facilitates and eventually reinstates drug self-administration. Repeated drug exposure also induces a process of sensitization of drug-induced stimulation of DA transmission in the NAc core. The precise significance of this adaptive change for the mechanism of drug addiction is unclear given the complexity and uncertainties surrounding the role of NAc core DA in responding but might be more directly related to instrumental performance.