A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use.

The effects of drugs and substances of abuse on central dopamine (DA) transmission studied by in vivo monitoring techniques have been examined and compared with those of conventional reinforcers and in particular with food. The similarities and differences in the action of drugs and conventional reinforcers on DA transmission can provide the basis for an hypothesis of the mechanism of drug addiction and compulsive drug use. This hypothesis states that drug addiction is due to excessive control over behaviour exerted by drug-related stimuli as a result of abnormal motivational learning induced by repeated drug exposure. Such abnormal motivational learning would derive from the repetitive non-habituating property of drugs of abuse to activate DA transmission phasically in the nucleus accumbens (NAc) 'shell'. Thus, activation of DA transmission by conventional reinforcers is under strong inhibitory control by previous exposure to the reinforcer (habituation); this, however, is not the case with drug reinforcers. Repetitive, non-adaptive release of DA in the NAc 'shell' by drugs of abuse would result in abnormal strengthening of stimulus-reward (incentive learning) and stimulus-response associations (habit learning) that constitute the basis for craving and compulsive drug use.