Fischer Rats Are More Sensitive Than Lewis Rats to the Suppressive Effects of Morphine and the Aversive Kappa-Opioid Agonist Spiradoline

Data have suggested that rats avoid intake of an otherwise palatable saccharin cue when paired with a drug of abuse, at least, in part, because the value of the taste cue pales in anticipation of the availability of the highly rewarding drug. Earlier support for this hypothesis was provided by the finding that, relative to the less sensitive Fischer rats, Lewis rats exhibit greater avoidance of a saccharin cue when paired with a rewarding sucrose or cocaine unconditioned stimulus (US), but not when paired with the aversive agent, lithium chloride. More recent data, however, have shown that Fischer rats actually exhibit greater, not less, avoidance of the same saccharin cue when morphine serves as the US. Therefore, Experiment 1 evaluated morphine-induced suppression of intake of the taste cue in Lewis and Fischer rats when the morphine US was administered subcutaneously, rather than intraperitoneally. Experiment 2 examined the effect of strain on the suppression of intake of the saccharin cue when paired with spiradoline, a selective kappa-opioid receptor agonist. The results confirmed that Fischer rats are more responsive to the suppressive effects of morphine than Lewis rats, and that Fischer rats also exhibit greater avoidance of the saccharin cue when paired with spiradoline, despite the fact that spiradoline is devoid of reinforcing properties. Taken together, the data suggest that the facilitated morphine-induced suppression observed in Fischer rats, compared with Lewis rats, may reflect an increased sensitivity to the aversive, kappa-mediated properties of opiates.