Figure 2.

During heroin abstinence, delta opioid receptor (DOR) activity prevents the emergence of anhedonia-like symptom, and kappa opioid receptor (KOR) activity mediates the development of social withdrawal. Heroin physical dependence (a and c) and emotional consequences of 4-week abstinence (b and d) were studied in DOR knockout (KO) mice and in their wild-type (WT) littermates (a and b), as well as in KOR knockout (KO) mice and in their wild-type (WT) littermates (c and d). Naloxone-precipitated withdrawal, as a measure of physical dependence achieved at the end of opiate exposure, and the analysis of emotional-like behaviors during protracted abstinence, after spontaneous heroin withdrawal had occurred (no naloxone), were performed in separate animal cohorts. In DOR KO mice, (a) acute heroin withdrawal (n=8–10 mice/treatment group/genotype) and (b, left panel) social avoidance following a 4-week abstinence period (n=14–15 mice/treatment group/genotype) are comparable to levels in WT controls. In contrast, (b, right panel) decreased sucrose preference specifically developed in DOR KO but not in WT mice during heroin abstinence (n=14–15 mice/treatment group/genotype). In KOR KO mice, (c) physical dependence to heroin is slightly decreased (n=8–10 mice/treatment group/genotype), and (d, left panel) social avoidance is fully prevented (n=16–18 mice/treatment group/genotype). No modification of sucrose preference (d, right panel) is observed for KOR KO mice under our experimental conditions (n=16–18 mice/treatment group/genotype). Values are mean±SEM.⁺p<0.001, ANOVA main effects of heroin; *p<0.01, post-hoc comparisons between the saline and heroin groups; ^#p<0.05, post-hoc comparisons between the saline and heroin groups within each genotype.