While it may seem difficult to differentiate the role of DA in brain reward mechanisms, a number of investigators have attempted to do so. Robinson et al.
] examined whether DA regulates liking, wanting, and/or learning about rewards during goal-directed behavior. The researchers tested genetically engineered dopamine-deficient (DD) mice for acquisition of an appetitive T-maze task with and without endogenous DA signaling. They established that DD mice treated with L-dihydroxyphenylalanine (L-dopa) performed similarly to controls on a T-maze task designed to measure liking, wanting, and learning about rewards. However, further experiments, which tested saline-, caffeine-, and L-dopa-treated DD mice on the T-maze, separated performance factors from cognitive processes, and the findings revealed that DA was not necessary for mice to like or learn about rewards, but it was necessary for mice to seek (want) rewards during goal-directed behavior. In essence, Robinson et al.
] demonstrated that reward learning could proceed normally in the brains of DD mice, even though they contained no DA at the time of learning, if the mice were given caffeine just before learning. Caffeine activated the DD mice by an unknown non-dopaminergic mechanism, allowing them to learn where to obtain food reward in a T-maze runway. Their reward-learning-without-DA was revealed on a subsequent test day, when DA function was restored by L-dopa administration. Robinson et al.
] concluded that DA was not needed for normal learning about rewards, nor for hedonic liking of rewards during learning, but rather specifically for a motivational wanting component of reward — incentive salience. These results agree with the findings of Davis [41
] (as previously cited) suggesting that DA is for “wanting” and opioids are for “liking”.
Wilson et al.
] systematically explored the role of neurotransmitters in “wanting” and “liking”. They tested rats following acute, systemic administration of drugs that globally enhance serotonin and noradrenaline (imipramine), DA (GBR 12909), and opioid (morphine) function in a behavioral task designed to measure wanting and liking. Imipramine augmented the effects of delay and taste on reward “wanting”, GBR 12909 attenuated the effects of delay on reward “wanting” and the effects of taste on reward “liking,” and morphine reduced the effect of delay on a measure of reward “wanting.” Since morphine failed to affect reward “liking,” but previously had been found to enhance reward “liking” in taste reactivity tests, and since DA seemed to affect both “wanting” and “liking,” these data underscore the complexity of this concept, as well as the need for more definitive research.
However, there is evidence that DA’s function is not one of inducing pleasure per se but instead is required for seeking pleasure. The findings of Schmidt et al.
] did not support the anhedonia hypothesis of central dopaminergic dysfunction as proposed other by investigators [50
]. Rather, affective flattening reflected by DA receptor sensitivity may result from the lack of an affective response towards reward-indicating stimuli. These findings indicated that patients with dopaminergic dysfunction were not unable to experience pleasure, but may have failed to be motivated by environmental stimuli to seek reward. The complex nature of reward mechanisms is further evidenced by the work of Mirenowicz and Schultz [53
], suggesting that DA neurons in monkeys were activated by unpredicted appetitive stimuli such as food and liquid rewards and by conditioned reward-predicting stimuli. They further found that in contrast to appetitive events, primary and conditioned aversive stimuli either failed to activate DA neurons or induced weaker responses than appetitive stimuli. Thus, DA neurons preferentially reported environmental stimuli with appetitive rather than aversive motivational value.
Of note, the idea that aversive and appetitive stimuli have some similar effects is an important element for the view that DA signals salience. However, it is not only DA that behaves in this way. Peptides such as corticotropin-releasing hormone also respond similarly to both types of stimuli, although the extent of the changes is not the same. Finally, Koob and Volkow [54
] in discussing the neurocircuitry of addiction, emphasized the role of both impulsivity and compulsivity leading to a tripartite addiction cycle involving three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation (craving). Impulsivity and compulsivity, as well as the various stages in the cycle, are tied to specific brain systems. Clearly, the picture is not a simple one.