Footshock stress potentiates cue-induced cocaine-seeking in an animal model of relapse

Abstract

Drug-associated cues and stress increase craving and lead to greater risk of relapse in abstinent drug addicts. This risk may be increased when these factors occur simultaneously. The current study examined whether the presentation of three different levels of intermittent footshock would trigger reinstatement or potentiate reinstatement of cocaine-seeking caused by conditioned cues. Male, Long Evans rats underwent daily i.v. cocaine self-administration, followed by extinction of lever responding in the absence of previously cocaine-paired cues. Reinstatement of cocaine-seeking was measured during presentation of cocaine-paired cues, following pretreatment with three levels of intermittent footshock (0.25, 0.5, and 0.75 mA), or after the combination of footshock and cues. Footshock at the 0.5 and 0.75 mA levels led to significant reinstatement when presented alone, and also potentiated the reinstatement triggered by the presentation of conditioned cues. These results demonstrate that while stress and drug-paired cues reinstate drug-seeking when presented in isolation, their interaction leads to potentiated reinstatement. Dual targeting of stress and cues is thus a critical consideration for treatment intervention in abstinent drug users.

Fig. 1

Mean number of responses on the active (black bars and squares) and inactive (white bars and triangles) levers on the last two days of cocaine self-administration (panel A) and the last seven days of extinction responding (panel B).

Fig. 2

Mean number of responses on the active (top panel) and inactive (bottom panel) levers on the last day of extinction responding (EXT), and conditioned-cue reinstatement tests (CUE), footshock stress reinstatement tests (FOOTSHOCK), and footshock plus conditioned-cue reinstatement test (FOOTSHOCK + CUE). Significant differences: *p<0.05 from EXT responding, #p<0.05 from CUE responding.