Regulatory effect of bee venom on methamphetamine-induced cellular activities in prefrontal cortex and nucleus accumbens in mice.

Our previous studies demonstrated that subcutaneous injection of bee venom (BV) into the Zusanli (ST36) acupuncture point, namely BV acupuncture, dose-dependently prevents conditioned place preference (CPP) induced by repeated injection of methamphetamine (METH) in mice. To expand on our observations, the present study was designed to determine the suppressive mechanisms of BV acupuncture in the development of METH-induced CPP by evaluating the changes in expression of ΔFosB, phosphorylated extracellular signal-regulated kinase 1/2 (pERK), and phosphorylated calcium/calmodulin-dependent protein kinase type II (pCaMKII) in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in mice. Pre-emptive treatment with BV at 30 min before repeated METH injection completely suppressed acquisition of CPP at the day 7 test session. METH-induced upregulation of ΔFosB and pERK in PFC and NAc was significantly reduced by BV pretreatment. Expression of pCaMKII was significantly elevated by METH in NAc and reduced in PFC. BV pretreatment reversed the changes of pCaMKII expression in PFC and NAc. These findings suggest that BV acupuncture may exert a suppressive effect on METH-induced addiction via regulation of signaling cascades of ΔFosB, ERK, and CaMKII in PFC and NAc.