Social stress is as effective as physical stress in reinstating morphine-induced place preference in mice

Rationale: Relapse to drug-seeking in abstinent heroin addicts and reinstatement in experimental animals are observed when exposed to drug-associated stimuli or cues, the drug itself, and stressful events. It has been shown that footshock-induced stress increases the rewarding effects of opiates, delays extinction, and induces the reinstatement of drug-seeking. However, the effects of social stress on the reinstatement of opiate-seeking after extinction has not been studied. Objectives: The role of physical (restraint and tail pinch) and social (social defeat) stressors on the reinstatement of morphine-induced conditioned place preference (CPP) was evaluated. Methods: Adult male OF1 mice were conditioned with 10, 20, or 40 mg/kg of morphine or saline. Only morphine-conditioned animals acquired CPP. All mice underwent extinction sessions until the CPP was extinguished. Then, the effects of physical or social stress on the reinstatement of CPP were evaluated. Morphine- and saline-conditioned animals were exposed to the respective stressor or control stress condition immediately or 15 min before reinstatement tests. In experiment 1, animals underwent restraint for 15 min. In experiment 2, animals were exposed to tail pinch or placed in a cage without any manipulation for 15 min. In experiment 3, animals performed an agonistic encounter with an isolated or anosmic mouse or were placed in a cage without any social contact or manipulation. Results: Restraint, tail pinch, and social defeat in an agonistic encounter with an isolated mouse produce the reinstatement of CPP in morphine-conditioned animals. Conclusions: These data demonstrate that social stress is as effective as physical stress in reinstating morphine-seeking.