Fig. 2.

The acute (A–C) and enduring (D–G) effects of social defeat stress on cocaine self-administration across phases of ‘the addiction cycle’. A cumulative histogram (A) shows increased rates of acquisition of cocaine self-administration (0.25 mg/kg/infusion; FR1) for rats 24 h after defeat (black bars) compared to non-defeated rats (white bars); data are divided into 12 h bins of total drug access (adapted from Tidey and Miczek, 1997). (B) The dose-effect function for cocaine on rate of responding (resp/min) maintained by an FR5 schedule; determined by three sessions per dose, and shown as mean ± SEM. Rats exposed to social threat from an aggressive resident for 60 min immediately prior to each session (black circles) show elevated rates of responding for lower doses in comparison to non-stressed controls (white circles). Triangles depict the response rates on an inactive lever (adapted from Miczek and Mutschler, 1996). (C) Re-exposure to cues predictive of impending social defeat produces reinstatement of cocaine seeking; shown are the active-lever responses during the maintenance phase of self-administration (“Maint”), extinction (“Ext”), and reinstatement (“Reinst”) following defeat-cue re-exposure (grey bars) or a non-stressful control condition (white bars). Data represent the mean ± SEM number of responses during the final three days of self-administration prior to the onset of stress sessions (“Maint”), the final three days of extinction (“Ext”), and a single reinstatement test session (“Reinst”). ****p < 0.0001 compared to extinction; #p < 0.05 compared to the control group (adapted from Manvich et al., 2016). (D) No differences in the acquisition of cocaine self-administration (0.75 mg/kg/infusion) one week after intermittent social defeat (grey circles) or handling (white circles), across ten days of training (adapted from Holly et al., 2016). (E) The dose-effect function for cocaine intake is elevated in mice previously exposed to intermittent social defeat prior to self-administration (grey circles), relative to handled controls (white circles). Individual data were averaged over two sessions; #p < 0.05, ##p < 0.01 compared to the control group (adapted from Han et al., 2015). (F) Total number of infusions during an unlimited access cocaine “binge” (0.3 mg/kg/infusion, FR1) are enhanced by exposure to intermittent social defeat stress (grey bars) prior to self-administration, compared to handled controls (white bars), in male and female rats. “Binge” terminated after 120 min without a cocaine infusion. #p < 0.05, ##p < 0.01 compared to the control group (adapted from Holly et al., 2012). (G) Upon return to the cocaine self-administration chamber after days of forced abstinence, defeated rats (dark grey bar) pressed the previously cocaine-paired lever significantly more than non-stressed animals (light grey bar) over a 3 h session. ***p < 0.001 compared to the control group (adapted from Holly et al., 2016). All data are expressed as mean ± SEM, with the exception of (A).