Figure 4.

Virally Cre-mediated recombination efficiently downregulates mu opioid receptors (MOR) in the dorsal raphe nucleus (DRN). (a) Experimental procedure. Independent animal cohorts (n=170 in total) were used for [³⁵S]-GTPγS binding, heroin physical dependence, and heroin abstinence (see Figure 5). (b) Pattern of eGFP expression following stereotactic infusion of AAV–eGFP shows viral diffusion restricted to the DRN. (c) Four weeks following surgery, MOR activity was significantly reduced in the DRN, as shown by lower DAMGO-induced [³⁵S]-GTPγS binding (n=14–16/group). In contrast, MOR signaling was preserved in the periaqueductal gray (d) or median raphe nucleus (e). Values are mean±SEM. ^#p<0.01, post-hoc comparison between the MOR^fl/fl and MOR cKO groups at each agonist concentration (M, molar concentration).