Testing the original anhedonia hypothesis

The original anhedonia hypothesis has been tested in studies of the effects of DA receptor antagonists and 6-OHDA lesions of DA neurons on operant and free-feeding measures of sucrose or saccharin reward. However, in spite of the large number of studies performed (reviewed by Di Chiara, 2000) the results obtained are compatible with any of the possibilities indicated above and therefore do not allow to be distinguished. 

Evidence consistent with this conclusion has been recently obtained by Pecina et al. (2003) in the genetically-engineered DAT knockdown mice, who carry a subtotal reduction in the expression of DAT which results in an increased steady-state level of extracellular DA (Pecina et al., 2003). Compared to the wild-type mice, the knockdown mice show faster running for food in a straight runway and an increased food intake, which results in an increased body weight. This increased motivation for food was not the result of increased rewarding properties of food as estimated from the hedonic reactions to intraoral infusion of sucrose. These studies therefore are consistent with the idea that sweet reward is independent from DA and that DA plays a role in the incentive, rather than the rewarding properties of food. 

Additional evidence against a simple hedonic function of the NAc DA transmission in food reward is provided by the observation that the behavioral effects of impairment of DA transmission on a concurrent operant and approach response for food are different 

Finally, intraaccumbens infusion of doses of D1 and D2 DA receptor antagonists that impair locomotion and rearing do not impair food intake and latency to feeding (Baldo et al., 2002). 

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