Factors that contribute to individual differences in responsiveness to cocaine and natural rewards in a reward comparison paradigm
Open Access
- Author:
- Schroy, Pearl Lee
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 28, 2006
- Committee Members:
- Patricia Sue Grigson, Committee Chair/Co-Chair
Robert Harold Bonneau, Committee Member
Matthew Mc Echron, Committee Member
Ralph Norgren, Committee Member
Richard Radcliffe, Committee Member - Keywords:
- cocaine
drug abuse
addiction
individual differences
saccharin
taste
reward comparison
corticosterone
inbred mouse strains
selective breeding
conditioned taste avoidance
conditioned taste aversion
anticipatory contrast
self-administration
sucrose
conditioning - Abstract:
- Abstract In rats, intake of an otherwise normally preferred saccharin solution is reduced when presentation of the saccharin solution is repeatedly followed by the administration of a drug of abuse, such as morphine, heroin, or cocaine. Recent data suggest that avoidance of the taste cue occurs because the rewarding properties of the saccharin are devalued in anticipation of the availability of the more rewarding drug of abuse. This ‘reward comparison’ paradigm serves as the first and only model of devaluation of natural rewards by drugs of abuse. Interestingly, while drug-induced suppression of saccharin intake is a robust phenomenon, clear individual differences have emerged. Indeed, approximately half of the Sprague-Dawley rats greatly avoid intake of the saccharin cue following taste-drug pairings (referred to as the large suppressers), while the other half of the rats (referred to as the small suppressers) do not. In addition, greater avoidance of the saccharin cue by the large suppressers is associated with greater saccharin cue induced elevations in circulating corticosterone (CORT) at test and, importantly, with greater cocaine self-administration behavior, as well. Although it is clear that humans also exhibit individual differences in the susceptibility to drug-taking behavior, it is not clear what mediates these differences in behavior or what factors contribute to the transition from recreational use to addiction. It is possible that individual vulnerability to addiction is mediated, in part, by greater drug craving or withdrawal when presented with conditioned drug cues. In the present paradigm, it is hypothesized that greater avoidance of the saccharin cue reflects better learning of the taste cue-drug association and this learning is facilitated by increased circulating levels of CORT. The present set of experiments addressed this hypothesis by employing behavioral and genetic methods to examine the nature of the differences observed in the large and small suppressers. The first few sets of experiments were designed not only to evaluate the nature of the CORT response in the phenomenon but also to determine whether the unconditioned CORT response to cocaine can predict which rats will go on to become large or small suppressers. The results of these experiments support the conclusion that greater elevations in both the conditioned and uncondtioned CORT response are associated not only with greater cocaine self-administration behavior but also with greater suppression in saccharin intake. Thus, higher levels of circulating CORT result in being more prone to drug-taking behavior and subsequent devaluation of a naturally rewarding saccharin solution. In a separate experiment, the general preference for sweets was tested for its predictive value in our paradigm. Greater intake of sucrose, however, was not associated with greater cocaine-induced avoidance of saccharin intake. The second set of experiments was designed to determine the extent to which genetic background would influence responsiveness to cocaine and subsequent devaluation of the saccharin reward. The results of a three generation selective breeding study revealed significant differences in the large and small suppresser lines by the second generation, suggesting that genetic makeup alone can influence behavior in the reward comparison paradigm. This conclusion was supported by the results of the final experiment that tested several inbred mouse strains (C57BL/6Ibg, DBA/2Ibg, and Sv129Ibg) in the reward comparison model that revealed significant strain differences in saccharin intake behavior. Taken together, these findings support that individual differences in cocaine-induced avoidance of saccharin intake are mediated by differences in genetic makeup, CORT, and learning (i.e., conditioning). Implications of these findings for drug addiction are discussed.