Cocaine-but not food-seeking behavior is reinstated by stress after extinction

Abstract

Reinstatement of drug-seeking behavior after extinction constitutes a potential animal model of relapse to drug abuse. In a typical reinstatement experiment, previously drug-trained rats undergo extinction during which responding is no longer followed by drug delivery. After significant extinction is observed, rats are then exposed to an event expected to reinstate drug-seeking behavior. Using this procedure, it has been recently reported that footshock stress leads to reinstatement of drug-seeking in heroin-trained, presently drug-free rats. The purpose of the present study was to assess the generality of this effect of stress. Here we report that 15 min of intermittent footshock (0.86 mA; 0.5 s on, with a mean off period of 40 s) reinstated selectively cocaine-seeking behavior after 14 extinction sessions (rats were previously trained on a FR1 TO 20 s to obtain cocaine at a dose of 0.25 mg/infusion). In contrast, under similar experimental conditions, the same stressor did not reinstate food-seeking in food-trained rats after seven extinction sessions (rats were previously trained on a FR1 TO 20 s to obtain six food pellets). Rather, when the basal level of responding was sufficiently high, footshock stress induced a significant suppression of the instrumental performance. These data are discussed in light of several behavioral mechanisms which may explain the specificity of stress in reinstating drug-seeking behavior and not food-seeking behavior.