Effects of stress modulation on morphine-induced conditioned place preferences in F344, LEW and Sprague-Dawley rat strains

Although stress appears to be directly related to drug use in a variety of outbred rat strains, this relationship seems indirect in inbred F344 and LEW rats, For example, the hyperresponsive F344 strain prefers drugs to a lesser degree than the hyporesponsive LEW strain. This indirect relationship with these selective strains is based on the correlation between hypothalamic-pituitary-adrenal axis reactivity and drug intake. To date, however, there are no reports on the direct effects of stress on drug use in these strains. The present study investigated the effects of increased (Experiment 1) and decreased (Experiment 2) stress on morphine-induced place preferences in male LEW, F344 and Sprague-Dawley (SD) rats. In Experiment 1, animals were exposed to an injection of methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate and 2-hr restraint stress followed by an assessment of morphine-induced place preferences (1, 4 or 10 mg/kg sc). In Experiment 2, animals were chronically exposed to the nonpeptide corticotropin releasing hormone type I receptor antagonist, antalarmin, prior to place preference training. Following stress, SD rats displayed potentiated place preferences relative to the non-stressed SD rats. Conversely, stressed LEW rats decreased their place preferences relative to non-stressed LEW rats. Stress did not affect the F344 strain. Following antalarmin, SD and LEW rats displayed a decrease in morphine-induced place preferences relative to their controls. Conversely, antalarmin potentiated these preferences in F344 rats. To account for data from the outbred Sprague-Dawley rats, as well as the LEW and F344 strains, the relationship between stress and drug use cannot be described as linear. The effects of stress (induction and reduction) on the rewarding effects of drugs are, instead, discussed in the context of a non-monotonic function, a model that is consistent with the continued use of the select rat strains as animal models of drug abuse.