Are Neurochemistry and Reinforcement Enough--Can the Abuse Potential of Drugs be Explained by Common Actions on a Dopamine Reward System in the Brain?

Many classes of drugs abused by man share with natural rewards the ability to incraese dopamine (DA) release in the nucleus accumbens (NAc) of the rat. However, this is unlikely to account for the rewarding effects of drugs of abuse, as NAc DA release is equally increased by aversive stimuli, and even by neutral stimuli paired together in a way that results in the formation of a conditioned association. Although NAc DA activity is thus increased by salient stimuli, and by salient associations between stimuli, it does not appear to be the case that the increase is critical for the formation of at least some types of conditioned associations. This makes it less likely that increased NAc DA activity underlies the reinforcing actions of these drugs in a general way. An action that two of these DA releasing drugs of abuse (amphetamine, nicotine) have in common is the disruption of latent inhibition (LI). In the case of amphetamine this action depends upon repeated administration, and, we believe, on the sensitization of DA release in NAc that this engenders. This sensitized DA release is qualitatively different, in that in contrast to the acute release, it is calcium dependent. Disruption of LI may therefore provide a biological marker for sensitization to amphetamine in rats. It may provide an account of the behavioural function of the NAc DA projections in terms of current relevance, or salience of stimuli. LI is a process in which prior experience of stimuli alters the way they enter into current learning: conversely its disruption represents the predominance of current stimulus contingencies over 'knowledge' based on prior experience. Thus disrupted LI may provide us with an animal model of better construct validity for the behaviour of humans dependent upon drugs than do increased locomotor activity, or even increased reward, in animals. [ABSTRACT FROM AUTHOR]