The role of dopamine in conditioning and latent inhibition: What, when, where and how?

It is well established that dopamine is released in the nucleus accumbens (NAC) in animals in rewarding or reinforcing situations, and widely believed that this release is the substrate of, or at least closely related to, the experience of reward. The demonstration of conditioned release of dopamine by stimuli conditioned to primary rewards has reinforced this view. However, a number of observations do not sit comfortably with this interpretation, most notably that dopamine is released equally effectively in NAC by aversive stimuli, and stimuli conditioned to them. Furthermore, additional release of dopamine is seen during conditioning, even if motivational stimuli of either type are not involved. It is suggested here that one important action of NAC dopamine release is to restore the salience of potential conditioned stimuli, when this has been reduced by prior un-reinforced experience. The paradigm of latent inhibition (LI) demonstrates a behavioural effect of this type, and extensive studies on the role of dopamine in LI have been undertaken by us and others. Those studies are reviewed here, together with some previously unpublished data, to demonstrate that (1) amphetamine disruption of LI is indeed a function of calcium-dependant dopamine release in the NAC at the time of conditioning; (2) other drugs acting on LI via changes in dopamine transmission act at the same locus; (3) the disruptive effect of indirect dopamine agonists on LI can be prevented by either D-1 selective receptor antagonists, or D-2 selective receptor antagonists. It is concluded that dopamine release in these very varied behavioural contexts (reward, punishment, conditioning, modulation of salience) must be differentiated in some way, and that this should be investigated. An alternative explanation, if they are not differentiated, would be that the release in fact does have the same functional significance in each case. We suggest that this common significance might be the broadening of attention to take in potentially conditionable stimuli, which have previously been devalued. (c) 2005 Elsevier Ltd. All rights reserved.