Rats will reduce intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse such as morphine or cocaine. This reduction in CS intake has led to the long standing assumption that drugs of abuse induce conditioned taste aversion learning via aversive properties. We have, however, published a number of papers over the preceding funding period arguing against this account. Indeed, the data support our alternative hypothesis that rats avoid intake of a saccharin CS following saccharin-drug pairings because they are anticipating rewarding, not aversive, drug properties. In support, our published data show that the suppressive effects of a rewarding sucrose solution, morphine and cocaine, but not those of the aversive agent, LiCI, are similarly affected by the value of the CS, the deprivation state of the rat, the strain of the rat, and a history of chronic morphine treatment. The paradigm, then, serves as the only model for the druginduced devaluation of natural rewards that plagues the human addict. Further, over the last funding period, we expanded the model to include drug self-administration and found that greater avoidance of the saccharin cue is associated with greater drug self-administration, greater reinstatement following abstinence, an increase in break point, and possibly, an increase in responding during extended access as well. Finally, additional preliminary data suggest that protection from cocaine self-administration may be conferred by the non-contingent (i.e., yoked) delivery of cocaine and by a history of brief access to a highly preferred natural reward. The proposed aims will: (I) Examine factors critical for drug-induced avoidance of the natural reward and subsequent drug self-administration; (II) Examine the protective effects of yoked drug delivery and natural reward using break point, a cocaine vs. water choice, and/or escalated responding; (III) Use a neurochemical, hormonal, and behavioral probe to determine the relative contribution of reward vs. aversion to cocaine-induced suppression of CS intake and, in so doing, begin to elucidate underlying substrates.
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