Abstract
Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA) axis activity. Yet, compared to Fischer 344 (F344) rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg) from saline using a two-lever, food-reinforced (FR10) procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine) test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.
Highlights
Stress enhances the behavioral effects of psychostimulant drugs such as cocaine [1,2,3]
Results of the present study show that acute stress differentially alters the behavioral effects of cocaine in a strain- and stress-selective manner
Exposure to one type of stressor enhances the discriminative stimulus effects of cocaine in Fischer 344 (F344) rats whereas exposure to the other stressors enhances response rates to cocaine in Lewis rats
Summary
Stress enhances the behavioral effects of psychostimulant drugs such as cocaine [1,2,3]. Acute exposure to stressors increases the place conditioning effects of stimulants [4], and promotes acquisition [5,6,7,8,9] and reinstatement [10,11] of stimulant self-administration. This interaction has important implications for vulnerability to drug addiction as well as relapse to use after abstinence. HPA axis function, mesolimbic dopamine system activity, and behavioral responses to cocaine differ between Lewis and Fischer (F344) inbred rats [17]. The present study sought to determine whether there are strain-selective effects of acute stress on the discriminative stimulus and response rate effects of cocaine in Lewis and F344 inbred rats
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