Reviewer 3's Review

The authors have produced a very detailed and interesting work, characterizing the ability of saccharin to produce an intensely rewarding state similar to that believed to underlie addiction to abused substances in humans and compulsively drug-seeking in animals. This work is preceded by a number of studies that have found significant effects of overconsumption of sugars and apparent cross-tolerance and cross-dependence between drugs-of-abuse and sugars. In addition, brain imaging studies of obese individuals have recently found adaptive changes previously demonstrated in substance-dependent individuals.

Two central conclusions, that saccharin may surpass cocaine in addictiveness (the title of the paper) and is able to surmount an established responding to a lever associated with cocaine reward, result from this study. The study examines this by lever preference in rats that may receive a saccharin solution or an i.v. cocaine infusion if responding in accordance with the assigned groups, S+/C-, S-/C+, or S+/C+.

N.B. These are the general comments made by the reviewer when reviewing this paper. Specific points addressed during revision of the paper are not shown.