Figure 5.

Conditional knockout of the mu opioid receptor (MOR cKO) in the dorsal raphe nucleus (DRN) prevents emergence of social avoidance during heroin abstinence. Naloxone-precipitated withdrawal (a) served as a measure of physical dependence achieved at the end of opiate exposure. Analyses of emotional-like behaviors during abstinence (b–d) were performed in separate animal cohorts, after they experienced spontaneous withdrawal from the chronic heroin treatment. MOR cKO in the DRN does not modify the severity of heroin physical dependence (n=6–7 mice/treatment group/virus type). In contrast, DRN MOR cKO in independent cohorts (n=9–13/treatment group/virus type) prevents the emergence of decreased social interactions (b) and decreases grooming duration (c), following a 4-week abstinence period. Finally, deleterious consequence of heroin abstinence on spatial working memory still manifested despite MOR cKO (d). Values are mean±SEM.⁺p<0.001, ANOVA main effects of heroin; ^‡p<0.001, ANOVA main effect of genotype; *p<0.001, post-hoc comparison between saline- and heroin-treated mice.