Morphine administration is a medical problem characterized by compulsive
opioid use that causes terrible negative consequences. The exact mechanisms of
morphine-induced dependence and
morphine withdrawal symptoms remain unclear. Recent studies have revealed that the upregulation of Wnt/β-
catenin signaling plays important roles in
morphine exposure and
morphine withdrawal. Secreted
frizzled-related protein 2 (Sfrp2) can prevent the activation of Wnt/β-
catenin signaling by competing with the
Frizzled receptor for Wnt
ligands. We conducted this study aimed to evaluate the effect of iatrogenic
trauma induced by stereotactic surgery and the protective effect of stereotaxic Sfrp2 injection on
morphine withdrawal symptoms in Male Sprague Dawley (SD) rats. Many techniques including western blot analysis and immunoprecipitation were used. Anxiety-related behaviors,
morphine withdrawal syndrome, and dendritic spines were also examined in male SD rats after
morphine treatment and stereotaxic injection of Sfrp2. Western blot results suggested that Wnt signaling was activated in the nucleus accumbens of SD rats suffering from
morphine withdrawal and that Sfrp2 attenuated the overexpression of Wnt signaling. Similarly, the withdrawal-like symptoms of
morphine dependent rats were abrogated by intracerebral Sfrp2 injection. The iatrogenic
trauma induced by stereotactic surgery showed no influence on the Wnt signaling and withdrawal-like symptoms. Moreover, the results of Golgi-cox staining and DiI staining indicated that the damage on proximal spine density caused by
morphine treatment was restored by intracerebral Sfrp2 injection. Together, the data presented here indicated that Sfrp2 abrogated the
neurological disorders and loss of proximal spine related with
morphine withdrawal via Wnt/β-
catenin signaling.