Robust effects of food deprivation as a relapse trigger: comparison to other stressors, and investigation of predictive individual traits in male and female rats.

Acute food-deprivation stress causes relapse to heroin seeking in male rats following punishment-invoked abstinence. Here we tested the generality of the effect by investigating whether forced swim, footshock, or restraint stressors would induce relapse to heroin seeking in male and female rats. In addition, we assessed whether individual traits could predict stress-induced relapse. Rats were first assessed in sucrose preference (SP) test, elevated plus maze (EPM), open field test (OF), and tail-flick (TF) test. Next, rats were trained to self-administer heroin (0.1 mg/kg/infusion, 6 h/day) under a seek-take chain schedule for at least 14 days. Heroin seeking was then punished with footshock (30% of trials; 0.2-0.6 mA) for 8 days. Once the rats achieved the abstinence criterion they were exposed to a stress condition [males: restraint (30 min), forced swim (20 min), intermittent footshock (0.5 mA, 10 min) or food deprivation (24 h); females: restraint (60 min), forced swim (4 min), or food deprivation (24 h)] before undergoing a heroin-seeking test. Female rats reached abstinence faster when heroin seeking was punished. Surprisingly, only food deprivation reliably induced relapse, and patterns of stress-induced relapse were similar in male and female rats. Individual differences in traits of sweet-solution preference, anxiety, novelty exploration or nociception did not reliably predict drug relapse. Our findings demonstrate the robustness of food deprivation stress as a trigger for relapse compared to the other stressors that were applied in this study.